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Structural Biology > Protein Folding > Flashcards

Protein Folding Flashcards

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1
Q

What is the primary process that proteins undergo after ribosomal synthesis?

A

Proteins will spontaneously adopt a well-defined 3D structure

This process is known as protein folding.

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2
Q

What does the energy landscape represent in protein folding?

A

The energy landscape shows free energy associated with the number of contacts/interactions in different conformational states

It illustrates how proteins fold into their native structures.

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3
Q

What types of contacts influence protein folding?

A

Native and non-native contacts

Native contacts decrease free energy, while non-native contacts do not.

Native contacts are typically stable and well-defined, and they play a key role in maintaining the protein’s structure and function.

Non-native contacts are interactions that are not present in the native state but may occur in the unfolded or partially folded states.
These contacts are typically transient or unstable and can lead to misfolding or aggregation of proteins.

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4
Q

What is the driving force behind protein folding?

A

The protein must make only native contacts to reach minimal possible free energy

This allows the protein to adopt its native structure.

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5
Q

What are the potential benefits of understanding protein folding?

A
  • Predict 3D structure of proteins from primary sequence
  • Understand and combat misfolding related to human diseases
  • Design proteins with novel functions

These applications can have significant implications in biotechnology and medicine.

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6
Q

What was the first step in Anfinsen’s experiment with ribonuclease?

A

Take ribonuclease and denature it with 8M urea and ß-mercaptoethanol (BME)

This unfolds the protein to a random coil state.

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7
Q

What happens after removing BME and urea in Anfinsen’s experiment?

A

Non-native disulfide bonds form, and no enzymatic activity is observed

The protein has not yet folded into its native state.

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8
Q

What is the purpose of adding a trace amount of BME in the experiment?

A

To denature non-native disulfide bonds

This allows the protein to recover enzymatic activity by reforming native disulfide bonds.

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9
Q

Fill in the blank: All information required to reach native structure is coded in the _______.

A

primary amino acid sequence

This conclusion is a key finding from Anfinsen’s experiment.

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10
Q

What are Intrinsically Disordered Proteins?

A

Proteins that have sequences preventing hydrophobic forces from driving folding

They make up ~30% of the total proteins in eukaryotic genomes.

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11
Q

What percentage of eukaryotic proteins are intrinsically disordered?

A

~30%

This indicates a significant presence in the proteome.

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12
Q

What is the relation between intrinsically disordered proteins and diseases?

A

Some are related to neurodegenerative diseases

Examples include Alzheimer’s and Parkinson’s diseases.

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13
Q

What defines protein stability in terms of folding?

A

Conformational stability given by the difference in G between denatured (D) and native (N) states

This is different from chemical stability.

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14
Q

What does chemical stability refer to?

A

The integrity of covalent bonds in the native state

It involves maintaining intact chemical bonds, oxidation states, and metal coordination.

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15
Q

What are disulfide bonds considered in terms of stability?

A

Borderline between chemical and conformational stability

Breaking covalent bonds can lead to changes in conformation.

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16
Q

Name one process that introduces chemical instability in proteins.

A

Deamination of Asn and GIn residues

This process converts them to Asp and Glu.

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17
Q

What happens to Asp residues at low pH?

A

Hydrolysis of the peptide bond occurs

This can lead to destabilization of the protein structure.

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18
Q

What is the effect of high temperatures on Methionine?

A

Oxidation to methionine sulfoxide

This can affect protein stability.

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19
Q

What does the elimination of disulfide bonds indicate?

A

Potential chemical instability

This can lead to loss of structural integrity.

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20
Q

What type of modifications can signal protein aging?

A

Deamination, hydrolysis, oxidation, and elimination of disulfide bonds

These modifications can be observed to track the age of proteins.

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21
Q

What is the relationship between structure and function in proteins?

A

Structure determines function

This principle is fundamental in biochemistry.

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22
Q

What is the significance of the native state of a protein?

A

It is more stable (lower G) than the denatured state

Stability influences protein functionality.

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23
Q

What are some diseases associated with intrinsically disordered proteins

A
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24
Q

What is conformation stability in proteins?

A

Protein’s ability to adopt/maintain well-defined conformation rather than a random coil.

Refers only to the formation of non-covalent bonds needed to achieve secondary/tertiary structures (hydrophobic interactions/VdW).

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25
Q

How is conformation stability judged?

A

Judged by phi & psi angles adopted by backbone atoms that do not induce steric clashes.

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26
Q

What do phi & psi angles do?

A

They rotate, allowing the polypeptide to assume various conformations.

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27
Q

What does the Ramachandran plot represent?

A

Only certain conformations are allowed as represented in the Ramachandran plot.

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28
Q

What is the significance of rotational values in protein conformation?

A

Rotational values do not fall in a single specific value but fall within certain ranges, indicating flexibility in secondary structures.

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29
Q

What is the equation for considering conformational stability?

A

ΔG = ΔH - TΔS

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30
Q

What are the two parameters that affect AG in conformational stability?

A

Change in entropy & change in enthalpy.

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31
Q

What contributes to a favourable ΔG

A

Favourable enthalpy contribution from intra-molecular side-chain interactions.

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32
Q

What is an example of an unfavourable ΔG

A

Unfavourable entropy change of folding a flexible polypeptide.

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33
Q

What is a favourable entropy change in protein folding?

A

Favourable entropy change from burying hydrophobic groups in the molecule (expulsion of water).

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34
Q

What contributes to a decrease in enthalpy during protein folding?

A

Different types of contacts such as hydrogen bonds, disulfide bonds, and hydrophobic interactions contribute to a decrease in enthalpy, which is a favorable decrease of AG.

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35
Q

How does protein folding affect entropy?

A

Folding reduces a huge number of possible conformations in the D state to a single N conformation, contributing to a decrease in entropy, which is an unfavorable increase of AG.

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36
Q

What is the main energetic contribution of protein folding?

A

The main energetic contribution comes from the release of ordered water from the exposed hydrophobic core due to the hydrophobic effect.

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37
Q

What is the average stability of small monomeric proteins?

A

The average stability is very small, only about 5-15 kcal/mol, compared to the energy of individual interactions, which requires thousands to form the N state.

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38
Q

Why are protein sequences selected to be not too stable?

A

Nature selects sequences that are not too stable because very stable proteins would be too rigid to perform any function, requiring flexibility for conformational changes.

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39
Q

What conditional parameters influence protein folding?

A

Parameters include pH, temperature, pressure, ionic strength, and crowding with other macromolecules.

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40
Q

What is the optimal condition for protein stability?

A

There exists an optimal condition (Topt/pHopt) in which the protein will be most stable and has the most enzymatic activity.

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41
Q

What effect does molecular crowding have on protein stability?

A

Molecular crowding in solutions that mimic the cellular environment can increase stability at higher temperatures.

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42
Q

What happens to the difference in ΔG between D and N states due to crowding?

A

Crowding causes more compaction if the proteins remain or become D, thus increasing the difference in ΔG between D and N states.

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43
Q

What types of interactions are involved in protein folding?

A

Covalent interactions, such as disulfide bond formation.
Are reversible.

Oxidation process can be intramolecular (within same proteins) or intermolecular (within different proteins )

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44
Q

What role do cellular enzymes play in protein folding?

A

Cellular enzymes, like protein disulfide isomerases, assist proteins in forming proper disulfide bonds.

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45
Q

What is compaction in protein folding?

A

Compaction refers to the folding of proteins to gain compactness, defined as the amount of surface area relative to a perfect sphere of comparable volume.

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46
Q

What is the compactness ratio of proteins with 101-150 amino acids?

A

The compactness ratio is approximately 1.5 relative to a perfect sphere.

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47
Q

What drives the compactness of proteins?

A

The internal residues that form a hydrophobic core, driven by the hydrophobic effect.

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48
Q

How do surface mutations affect protein folding?

A

Most surface mutations can be accommodated without affecting the fold, such as the modification of Lys residues in RNAse A to poly-Ala.

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49
Q

What happens when mutations occur in the hydrophobic core?

A

Mutations in the hydrophobic core can have strong effects on protein folding.

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50
Q

What is the hierarchy in protein folding?

A

Proteins fold using a hierarchy where subdomains form spontaneously and interact to create stable, independent folding units.

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51
Q

What forms the tertiary structure of proteins?

A

Tertiary structure forms when multiple domains pack together.

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52
Q

How are protein structures adaptable to

A

Protein structures, including hydrophobic cores, are adaptable, allowing mutations to be accommodated with local shifts in packing.

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53
Q

Can you give an example of adaptability in protein structures?

A

An example is the mutagenesis of T4 lysozyme.

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54
Q

What percentage of amino acid sequence identity between proteins typically results in the same overall fold?

A

20%

This indicates that proteins can maintain similar structures despite having significant sequence variability.

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55
Q

What can be deduced about protein residues based on the observation of different structures at 88% sequence identity?

A

Only certain residues are key to maintain the native conformation of a particular shape

The residues that are crucial for maintaining the structure are often highlighted in studies.

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56
Q

What are some techniques used to measure protein stability?

A
  • Absorbance
  • NMR
  • Differential Scanning Calorimetry (DSC)
  • Monitor Catalytic activity
  • Circular Dichroism
  • Protein Denaturation

These methods help differentiate between the native (N) and denatured (D) states of proteins.

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57
Q

In absorbance measurements, what are chromophores?

A

Molecules that can absorb light at a particular wavelength

Chromophores give rise to observable colors of light in the wavelength they do not absorb.

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58
Q

Which amino acid side chains are commonly used as chromophores?

A
  • Tryptophan (Trp)
  • Tyrosine (Tyr)
  • Phenylalanine (Phe)

These aromatic side chains are effective in absorbance measurements due to their light-absorbing properties.

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59
Q

What is the most commonly used chromophore for measuring protein stability and why?

A

Fluorescence, because it provides the greatest change in signal between the N and D state

Fluorescence shows significant differences in emission maximum and intensity between the two states, leading to high signal-to-noise ratio (SNR).

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60
Q

True or False: The difference in absorbance between the native and denatured conformations is usually large for most proteins.

A

False

For most proteins, the difference in absorbance is very small, making it applicable only in specific cases.

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61
Q

Why may proteins with high seq identity still exhibit different chemical shifts

A

They differ due to different environments caused by different conformations

Even proteins with high sequence identity can exhibit variations in chemical shifts.

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62
Q

Fill in the blank: Techniques to measure protein stability must differentiate between _______ and D states of the protein.

A

N

N refers to the native state of the protein.

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63
Q

What are the properties that affect protein folding

A

Covalent interaction
Compaction
Hierarchy
Adaptability
Sequence versatility

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64
Q

What is protein denaturation?

A

Loss of structural integrity and activity of proteins.

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65
Q

What are common causes of protein denaturation?

A
  • Extreme temperatures
  • pH extremes
  • Organic solvents
  • Chaotropic agents
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66
Q

How does extreme cold affect proteins?

A

Causes a small detectable fraction to unfold.

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67
Q

What effect does heat have on proteins?

A

Can unfold all molecules within a solution, providing a greater signal.

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68
Q

Which agents are considered chaotropic?

A
  • Urea
  • Guanidinium hydrochloride
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69
Q

What is the role of chaotropic agents in protein denaturation?

A

Disrupt the hydrogen bonding network between water molecules, reducing protein stability.

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70
Q

What type of curve is observed during protein denaturation?

A

A sigmoidal curve as the fraction of protein becomes unfolded.

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71
Q

What does Tm represent in protein studies?

A

The specific point at which 50% of proteins are in denatured state and 50% in native state.

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72
Q

What is Circular Dichroism (CD) used for?

A

Measures the molar absorption difference due to proteins’ ability to absorb circularly polarized light.

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73
Q

What is the formula for calculating the difference in absorption in Circular Dichroism?

A

L - left
R- right

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74
Q

What does the term ‘hydrophobic effect’ refer to in protein stability?

A

The tendency of non-polar substances to aggregate in aqueous solution to minimize their exposure to water.

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75
Q

True or False: Not all proteins denature at pH extremes.

A

True

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76
Q

What is the Tm, [D]50% value used for

A

Used to compare protein stability against extreme conditions.

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77
Q

How does circularly polarised light arise

A
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78
Q

What happens when the horizontal and vertical components of light are out of phase?

A

They produce circularly polarized light.

The phase difference is typically 90°.

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79
Q

What is the direction of rotation for a right-circularly polarized light wave?

A

clockwise.

This is observed when the electric vector is rotating in that direction.

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80
Q

What determines whether circularly polarized light is left-handed or right-handed?

A

The direction of rotation of the electric field vector determines the handedness:
Clockwise → Right-Handed
Counterclockwise → Left-Handed

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81
Q

What happens to circularly polarized light when it is absorbed by a medium?

A

It continues to have smaller amplitudes.

The absorption leads to a decrease in intensity.

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82
Q

What is Circular Dichroism?

A

It arises due to a protein’s differential ability to absorb left and right circularly polarized light.

This results in different amplitudes for the two directions of circularly polarized light.

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83
Q

What type of polarization results from the combination of left and right circularly polarized light after absorption by a protein? (When diff amounts of each absorbed )

A

Elliptical polarization.

This occurs when the two circularly polarized lights are absorbed differently.

The unequal absorption can result in a combination of the remaining left and right circularly polarized light, leading to elliptical polarization. The phase and amplitude differences between the two components create the elliptical shape.

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84
Q

What is the result when a protein absorbs equal amounts of left and right circularly polarized light?

A

The resulting amplitude remains linearly polarized.

This means there is no differential absorption effect.

Linear polarization refers to a state of light where the electric field oscillates in a single plane

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85
Q

Fill in the blank: When a sample absorbs left and right circularly polarized light equally, the detected light can be represented as _______.

A

Linearly polarized.

The detection results indicate that the net effect of absorption does not favor one circular polarization over the other.

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86
Q

What is the phase difference required for circular polarization?

A

90°.

This phase difference is crucial for the creation of circularly polarized light.

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87
Q

What type of light do proteins preferentially absorb?

A

Left or right circularly polarized light

Proteins have different refractive indices and extinction coefficients for left and right circularly polarized light.

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88
Q

What happens to the amplitudes of circularly polarized light after absorption by proteins?

A

They have different amplitudes; the light preferentially absorbed has a smaller amplitude

This results in elliptic polarization.

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89
Q

What is the result of combining circularly polarized light with different amplitudes?

A

Elliptic polarization

90
Q

If a wave’s electric vector appears to be rotating counterclockwise, what type of polarization is it?

A

Right-elliptic polarization

This occurs when viewed by an observer.

91
Q

What can be monitored and recorded in a spectra using circularly polarized lights?

A

CD (Circular Dichroism)

This is done by varying the wavelengths of circularly polarized lights in the far-UV range (190-240 nm).

92
Q

What structures can be obtained from CD spectra

A

Different secondary structures including random coil

These spectra vary based on the structure of the protein.

93
Q

What indicates the signature CD for a secondary structure?

A

The wavelength with the greatest difference between CD of a regular secondary structure and CD of random coil

This signature is different for each secondary structure.

94
Q

Fill in the blank: The electric vector of a right-elliptic polarized light appears to rotate _______.

A

Counterclockwise

95
Q

True or False: The direction of propagation affects the ellipticity of the polarized light.

A

True

96
Q

What is the range of wavelengths in the far-UV for monitoring CD?

A

190-240 nm

97
Q

What happens to circularly polarised light after absorption by the protein

A

Proteins, being chiral, often absorb left- and right-circularly polarized light differently. This phenomenon, known as circular dichroism (CD), leads to an imbalance in the intensities of the two polarizations. If left- and right-circularly polarized light are not equally absorbed, the light that emerges from the sample no longer maintains a perfect circular polarization. Instead, it becomes elliptically polarized.

98
Q

How can folding/unfolding of the protein be monitored

A
99
Q

What are the pros and cons of using CD to monitor protein folding

A
100
Q

What does the Levinthal paradox state?

A

Finding the native folded state of a protein by a random search among all possible configurations can take an enormously long time due to proteins’ amino acid combinations allowing multiple possible conformations. However, proteins can fold in seconds or less.

Most single-domain proteins fold in the millisecond/second timescales.

101
Q

What conclusion can be drawn from the Levinthal paradox?

A

The folding of a protein is not the result of a random search; it must follow well-defined folding pathways.

102
Q

What is the energy landscape in protein folding?

A

Protein folding towards the native state (minimum G) is funneled by local minima (local low energy conformations) rather than by sampling random conformations until a minimum is reached.

103
Q

What can happen if too many local minima exist during protein folding?

A

A very stable local minimum can decelerate folding and even prevent the protein from reaching its native state due to a high energy barrier to overcome.

104
Q

What are the implications of local minima having exposed hydrophobic regions?

A

Conformations at the local minima can interact with other components in the cell or lead to protein aggregation, which is toxic to the cell.

105
Q

What is the significance of measuring protein folding pathways?

A

Folding that goes directly from the denatured (D) state to the native (N) state without any stable intermediates is significant.

106
Q

What technique is used to study protein folding pathways?

A

Fluorescence resonance energy transfer (FRET) is used in single-molecule experiments.

107
Q

How does FRET work?

A

FRET utilizes a donor and acceptor dye; the donor dye absorbs light at a certain wavelength and emits it at another, which is in the same range as the wavelength absorbed by the acceptor dye.

108
Q

What happens to FRET efficiency as a protein denatures?

A

As the protein denatures, the structures and chromophores become far apart, leading to reduced FRET efficiency.

109
Q

What does a jump in FRET efficiency indicate?

A

A jump in FRET efficiency can be used to observe folding and unfolding events.

110
Q

What occurs in the N state during FRET?

A

Introducing incident blue light onto a sample in the N state will result in emitted red light due to the close distance of the chromophores, thus high FRET efficiency.

111
Q

What occurs in the D state during FRET?

A

In the D state, the two chromophores are further apart, resulting in green fluorescence emitted by the donor dye when blue light is introduced, leading to low FRET efficiency.

112
Q

What methods can be used to measure protein folding pathways

A

FRET
Stopped flow device
Phi value analysis

113
Q

What happens if two chromophores are close in space in FRET

A
114
Q

What is the purpose of a stopped flow device?

A

To study a population of molecules

It utilizes rapid mixing to initiate refolding or unfolding of proteins.

115
Q

What are the two syringes used in a stopped flow device?

A

One with protein mixed with denaturants and the other with buffer

Denaturants can include substances like urea or HCl.

116
Q

What happens when the piston of the stopped flow device is pushed?

A

It rapidly introduces the two solutions to each other, resulting in refolding of denatured proteins.

117
Q

What is the role of the capillary tube in a stopped flow device?

A

The mixed solution travels through it to be analyzed by a light source and a fluorescence detector.

118
Q

How does the stopped flow device detect changes in protein fluorescence?

A

By using a light source to excite chromophores and a fluorescence detector that can be moved to vary mixing time.

119
Q

What can be measured downstream to observe changes in protein behavior?

A

Change in absorbance over mixing time using a movable spectrophotometer.

120
Q

How is unfolding observed in the stopped flow device method?

A

The content of the syringes is switched: protein + buffer in one and a denaturing agent in the other.
Will cause denaturation

121
Q

What is the significance of the device’s death time?

A

It is the time it takes to mix the two samples, leading to a region with no data.

122
Q

What type of curve can experimental data be fit to in a stopped flow analysis?

A

A single exponential curve for 2-state folding.

123
Q

What does observing the residual plot of stopped flow device data help determine?

A

The number of intermediates/states the protein goes through.

124
Q

What does a single exponential fit indicate in protein folding?

A

A 2-state folding process (denatured to native).

125
Q

What does a double exponential fit correspond to in protein folding?

A

1 intermediate in a 3-state folding process (D-I-N).

I = intermediate

126
Q

What does a triple exponential fit indicate in protein folding?

A

2 intermediates in a 4-state folding process (D-I-I-N).
I = intermediate

127
Q

Fill in the blank: The stopped flow device utilizes _______ to initiate refolding/unfolding.

A

rapid mixing

128
Q

What is the location of the transition state (TS) in relation to the denatured (D) and native (N) states?

A

The TS is located between the D and N states.

129
Q

Why can’t the transition state (TS) be observed directly?

A

The TS has a high Gibbs free energy (G), is extremely short-lived, and cannot be observed using techniques like NMR or crystallography.

130
Q

What role does the transition state (TS) play in protein folding?

A

The TS is the rate-limiting step of protein folding and can determine if a protein can transition from the denatured (D) state to the native (N) state or vice versa.

131
Q

What is required for the formation and stabilization of the transition state (TS)?

A

The formation and stabilization of the TS require a number of critical contacts involving specific amino acids.

132
Q

What effect does a mutation that impacts the stability of a protein structure have on Gibbs free energy (G)?

A

It will result in an increase in G.
Mutation in protein aa residue will always cause change in G of N state

133
Q

What indicates that a mutated residue is important for transition state (TS) formation?

A

A mutation that changes G in both TS and N indicates that the mutated residue is important in TS formation.

134
Q

What is the Phi value in the context of transition state (TS) analysis?

A

The Phi value is the ratio of the difference in stability (G) between the mutant TS and the wild-type TS to the difference in stability (G) between the mutant N and the wild-type N.

135
Q

What does a Phi value of 1 signify about a mutated residue?

A

A Phi value of 1 indicates that the mutated residue is native-like and structured in the TS.

136
Q

What does a Phi value of 0 indicate about a mutated residue?

A

A Phi value of 0 means the mutated residue is non-native-like and/or unstructured in the TS.

137
Q

What does an intermediate Phi value (e.g., 0.5) suggest about a residue’s contribution to the transition state (TS)?

A

It suggests that those residues contribute to the TS structure but are not exactly native-like.

138
Q

How can Phi value analysis be utilized in protein studies?

A

Phi value analysis can determine the structure or refine the structure of the TS by identifying critical contacts made by specific amino acid residues.

139
Q

What type of mutations are preferred in Phi value analysis and why?

A

Conservative deletion mutants are preferred because they introduce subtle changes that decrease stability without affecting the structure of the native (N) state.

140
Q

Why is mutation to alanine commonly used in Phi value analysis?

A

Mutation to alanine is common because it removes all side chains except from the beta carbon, minimizing structural changes.

141
Q

What is the relationship between folding rate and the free energy difference between the transition state (TS) and the denatured state (D)?

A

There is a direct correlation; a more stable TS results in a more negative free energy difference between TS and D, leading to faster folding rates.

142
Q

How do you calculate the phi value

A
143
Q

What is the structure of the ribosome

A
144
Q

What are the 3 phases of protein synthesis

A
145
Q

How does a cell deal with molecular crowding

A
146
Q

What are chaperone proteins

A
147
Q

List the different types of chaperone proteins

A

Bacterial trigger factor
HSP70
Chaperonins
HSP90
Nucleoplasmins
Protein disulphide isomerase
Peptide prolyl isomerase

148
Q

What are the characteristics of bacterial trigger factor chaperone proteins

A
149
Q

What are HSP70 chaperone proteins

A
150
Q

What are chaperonins

A
151
Q

What are HSP90 chaperone proteins

A
152
Q

What are nucleoplasmin chaperone proteins

A
153
Q

Where do newly synthesised proteins leave from the ribosome

A
154
Q

What are trigger factors + structure

A

To avoid formation of toxic aggregates after protein leaves ribosome

155
Q

What is the role of the N terminal domain of trigger factors

A
156
Q

What is the role of the C terminal domain of trigger factors

A
157
Q

What is the role of the PPIase domain of trigger factors

A
158
Q

What are the characteristics of trigger factors

A
159
Q

What are heat shock proteins and their roles

A
160
Q

What is the role of HSP70 in eukaryotes

A
161
Q

Describe how HSP70 carried out its role

A
162
Q

What is the GroEL/GroES complex

A
163
Q

Describe the GroEL/GroES cycle

A
164
Q

What are the features of the GroEL/GroES complex

A
165
Q

What are the characteristics of HSP90

A

Function can be affected by different types of PTMs (e. g. phosphorylation, acetylation)
Details of substrate binding and mechanism still being studied

166
Q

Describe the steps for HSP90 activity

A
167
Q

What are the characteristics of Protein disulphide isomerase (PDI)

A
168
Q

Describe the process of PDI activity

A
169
Q

What are the characteristics of PPI

A
170
Q

Why are proteins recycled

A
171
Q

What does orthine do

A
172
Q

What does p53 do + it’s half life

A
173
Q

Name some proteins with a longer half life

A
174
Q

Name the different protein turnover mechanisms

A
175
Q

How is ubiquitin added to a protein

A
176
Q

What are E3 ligases

A
177
Q

what is the proteasome

A
178
Q

What is the structure of the proteasome

A
179
Q

What is the mechanism of degradation by the proteasome

A
180
Q

Summarise the overall ubiquitin-proteasome pathway

A
181
Q

Describe the process of the bacterial ubiquitin-proteasome pathway

A
182
Q

Describe the process of the aggresome-autophagy pathway

A
183
Q

Describe the process of chaperone-mediated autophagy

A
184
Q

What are the external factors that affect protein quality

A
185
Q

What are the internal factors that affect protein quality

A
186
Q

How can oxygen and nitrogen radicals modify amino acids within proteins and what could this modifications cause

A
187
Q

What is the cellular response to oxidative stress 0.5 to 5 hours after exposure

A
188
Q

What is the cellular response to oxidative stress 5 to 48 hours after exposure

A
189
Q

What could happen to unfolded proteins after synthesis

A
190
Q

What is an amyloid *

A

An amyloid is an aggregated protein structure characterized by its highly ordered, beta-sheet-rich fibrillar morphology. Amyloids are formed when normally soluble proteins misfold and self-assemble into long, insoluble fibrils. These fibrils stack together into highly stable and rigid structures that can accumulate in tissues, leading to various diseases

191
Q

What is the amyloid formation pathway

A
192
Q

What are amyloidogenic precursors

A
193
Q

What are prefibrillar oligomers

A
194
Q

What are amyloid fibrils

A
195
Q

What is the structure of amyloid fibres

A
196
Q

Why are structures made from amyloid fibres important

A
197
Q

Name some diseases caused by misfolded proteins

A

Alzheimer’s
Parkinson’s
Prion disease

198
Q

Explain roughly how Alzheimer’s occurs

A
199
Q

What 2 proteins is Alzheimer’s associated with

A

Associated with the aggregation of amyloid-beta-peptide and tau

200
Q

What is amyloid-beta-peptide,

A
201
Q

What is tau

A
202
Q

What is Parkinson’s and what protein is it associated with

A
203
Q

What are the normal functions of alpha synuclein

A
204
Q

What are the affects of alpha synuclein aggregation

A
205
Q

What is prion disease and what protein is it associated with

A
206
Q

How does prion disease occur

A
207
Q

What are intrinsically disordered proteins

A
208
Q

What are the characteristics of disordered proteins

A
209
Q

What is the energy landscape of intrinsically disordered proteins

A
210
Q

What is the protein quartet model

A
211
Q

What are the 4 different types of protein structures and describe them

A
212
Q

How can the four different types of protein structures be distinguished

A
213
Q

What is the easiest way to distinguish an IDP

A
214
Q

Why can’t crystallography be used to identify IDPs

A
215
Q

How can NMR be used to identify IDPs

A
216
Q

What secondary structures of IDPs can be identified using NMR

A
217
Q

How can circular dichroism be used to distinguish guys between the 4 different types of protein structures

A
218
Q

What are the functions of IDPs

A
219
Q

How is Alpha synuclein an example of intrinsically disordered protein function

A
220
Q

What are the characteristics of spider silk proteins

A
221
Q

How can FRET be used to determine regions involved in protein-protein interactions of ProTalpha and H1

A
222
Q

How can NMR be used to deduce the residues involved in ProTalpha binding

A

Structural Biology (8 decks)

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