Biochem Midterm I - Oct 11th Flashcards

Question

- The formation of micelles or bilayers are _______ ______ - The size of a micelle and the number of surfactant molecules it contains are influenced by the size of the ____ ____ group and the length of the ____ ____.

Answer 1

thermodynamically favourable polar head nonpolar tail

Answer 2

smaller larger

Answer 3

- A special group of amphiphile: the molecule which has both polar and nonpolar segments - Structurally the simplest version of lipids - A detergent forms micelles in water only when its conc. is above the critical micellar concentration (CMC) - Depending on the head group, the detergents can be divided into ionic and non-ionic. - _Ionic detergents_ are more powerful at solubilising proteins, or for washing your clothes

Answer 4

Molecules that contain both polar and nonpolar groups (i.e fatty acids)

Answer 5

_Amphiphilic_ refers to a molecule that has both hydrophilic (water-attracting) and hydrophobic (water-repelling) parts and has an affinity for both polar and non-polar environments. It's typically used in the context of how molecules interact with water and oils, such as surfactants. _Amphipathic_ also refers to molecules with both hydrophilic and hydrophobic regions, but the term emphasizes the structural division of these regions within the molecule. It’s often used in a biological context, such as describing lipids in membranes.

Answer 6

pH = -log[H+] pKw = pH + pOH = 14 HA ⇌ H+ + A-

Answer 7

This denotes the concentration of hydrogen ions (protons) in a solution. It is a measure of acidity, and higher [H+] concentrations correspond to lower pH values.

Answer 8

This represents the concentration of the undissociated weak acid, where "HA" signifies the acid itself (e.g., acetic acid). It is the form of the acid that is not dissociated into ions in solution.

Answer 9

This indicates the concentration of the conjugate base of the weak acid, formed when the acid donates a proton. For example, if HA is acetic acid, then [A−] would refer to the acetate ion (CH3COO-).

Answer 10

An acid that IS NOT completely dissociated in the water solt.

Answer 11

The solt. which contain at least one pair of weak acid and its conjugate base - The best buffering capacity occurs when there is [HA] = [A-], in other words when pH= pKa - pKa changes when solt. temp changes

Answer 12

Ka = [H+][A-]/[HA] - A higher Ka value indicates a stronger acid (greater dissociation), while a lower Ka value indicates a weaker acid - Usually it is products on top and reactants on the bottom

Answer 13

The titration of phosphoric acid (H3PO4), a triprotic acid, involves sequentially adding a strong base, such as sodium hydroxide (NaOH), to determine the pKa values corresponding to its three dissociation steps. Each dissociation yields a conjugate base: H2PO4−, H2PO42- and PO43−, with distinct equivalence points observable in the titration curve. The resulting pH changes at each equivalence point are indicative of the buffer regions, reflecting the acid-base equilibrium of the phosphate species. The titration curve typically displays a characteristic sigmoidal shape, allowing for the precise determination of pKa values and the acid's overall strength.

Answer 14

- Equivalence Points: The inflection points on the sigmoidal curve indicate the volumes of titrant where specific protons from phosphoric acid have been completely neutralised. - Buffer Regions: Between equivalence points, the curve shows gradual pH changes, reflecting the buffering capacity of the acid-base pairs present. - Titration Progress: The x-axis illustrates the relationship between titrant volume and pH changes, helping to assess the strength and behaviour of the acid throughout the titration.

Answer 15

Dipolar (containing both + and - charges but overall neutral) amino acids. The predominant form of amino acids in pH neutral conditions. The + group is NH3+ and the - group is COO-. This dual charge allows zwitterions to exhibit unique properties, such as high solubility in water and the ability to act as both acids and bases, influencing their behaviour in biological systems and chemical reactions.

Answer 16

Asp Glu Lys Arg His

Answer 17

Ser Thr Cys Asn Gln Seriously Thrown Cysts Assassinate Gringos

Answer 18

Gly Ala Pro Val Leu Ile Met Gliding Allow Professionally Valued Losers Illegitimate Methods

Answer 19

Phe Tyr Trp Phoenix's Try Trips

Answer 20

Gly Ala Pro Val Leu Ile Met Phe Tyr Trp Gliding Allow Professionally Valued Losers Illegitimate Methods for Phoenix's Trying Trips

Answer 21

Ser Thr Asn Gln Some Asinine Threesomes Golong

Answer 22

Lys Arg Asp Glu Asparagus Glue Lyses Argentinians

Answer 23

His Tyr Cyst His Tyred Cyst

Answer 24

The cyclic nature of proline results in a rigid structure that restricts the flexibility of the polypeptide chain. Unlike other amino acids, _proline's side chain is part of the backbone,_ limiting the possible torsion angles around the peptide bond

Answer 25

glycine cystine Isoleucine

Answer 26

1. GABA 2. Histamine 3. Dopamine or Thyroxine

Answer 27

Two molecules of the tripeptide glutathione (composed of glutamate, cysteine, and glycine) combine to form glutathione disulfide (GSSG) through the oxidation of cysteine’s thiol groups, creating a covalent disulfide bond. This reversible dimerization is key to cellular redox balance. Reduced glutathione (GSH) functions as an antioxidant, while its oxidised form (GSSG) can be converted back to GSH by glutathione reductase, maintaining redox homeostasis during oxidative stress.

Answer 28

phosphorylated acetylated hydroxyproline posttranslational

Answer 29

- By formation of peptide bonds, the ionisable states of -NH2 and COOH are lost and only one -NH2 and one COOH group are left at the end (_side chain may also contain the ionisable groups_) - The alpha carbon and the peptide bonds form the backbone of a polypeptide

Answer 30

(like those of leucine, isoleucine, and phenylalanine) tend to cluster together in the interior of proteins, helping to stabilise the protein’s three-dimensional structure.

Answer 31

(like those of serine, threonine, and glutamine) often participate in hydrogen bonding and are usually found on the protein surface, interacting with water or other polar molecules.

Answer 32

(like lysine, arginine, and glutamate) play critical roles in forming salt bridges, participating in enzyme catalysis, or interacting with the surrounding environment, depending on their charge at physiological pH.

Answer 33

The isoelectric point (pI) is the pH at which a molecule, such as an amino acid or protein, carries no net electrical charge. At this pH, the concentrations of positively and negatively charged forms of the molecule are equal, resulting in a state of electrical neutrality.

Answer 34

anode cathode Below above

Answer 35

- An amino acid side chain is ionisable if it contains functional groups that can gain or lose protons, such as carboxyl (-COOH), amino (-NH₂), sulfhydryl (-SH), or imidazole groups. - Common ionisable amino acids include aspartate, glutamate, lysine, arginine, histidine, cysteine, and tyrosine. Whether the side chain ionises depends on its pKa value and the surrounding pH

Answer 36

1. Identify the pKa Values: Most amino acids have two main ionisable groups: - The carboxyl group (COOH), typically with a pKa around 2.0. - The amino group (NH3+), typically with a pKa around 9.0. 2. Use the Formula: The pI is calculated using the average of the pKa values of the groups that are protonated at the pH where the molecule is neutral: pI = (pKa1 + pKa2)/2

Answer 37

1. Identify the pKa Values: For amino acids with ionisable side chains (like aspartic acid or lysine), you need to include the pKa of the side chain. 2. Determine the Relevant pKa Values: If the pH range of interest spans the pKa of the side chain, use the pKa values for both the terminal amino and carboxyl groups and the side chain. 3. Use the Average of the Relevant pKa Values: The pI is calculated by averaging the pKa values of the ionisable groups that flank the neutral species. So if pKa 1 = 2.0, pKa 2 = 4.0 and pKa 3 = 9.0 pI = (2.0+4.0+9.0)/3 = 7.5

Answer 38

- A technique for precipitating proteins by increasing salt concentration, usually with ammonium sulphate. As salt concentration rises, water molecules are drawn to the salt ions, reducing the protein's hydration shell and solubility, causing aggregation and precipitation. - Used in the initial steps of protein purification to remove unwanted proteins and concentrate the target protein.

Answer 39

- A purification method used to remove small molecules, like salts or impurities, from a protein solution by using a semipermeable membrane which allows small molecules to pass through while retaining larger molecules, such as proteins. The protein solution is placed in a dialysis bag or tube, submerged in buffer, where small molecules diffuse into the buffer, leaving the proteins inside. - This method is commonly applied after salting out to remove excess salts or to exchange buffers after other purification steps

Answer 40

- A purification technique that separates proteins based on their physical or chemical properties as they move through a column filled with a solid matrix. Types include ion exchange, size-exclusion (gel filtration), hydrophobic interaction, and affinity chromatography. - Proteins are applied to the column and pass through the stationary phase, where separation occurs based on charge, size, hydrophobicity, or affinity to a ligand, depending on the method used. - It is widely used in protein purification and can be tailored to the protein's specific characteristics.

Answer 41

- Separates proteins based on their net charge at a specific pH. - In anion exchange, negatively charged proteins bind to a positively charged matrix, while in cation exchange, positively charged proteins bind to a negatively charged matrix. - Proteins are eluted by increasing salt concentration or adjusting pH to disrupt electrostatic interactions. - It is commonly used to purify proteins with known charge properties, such as separating proteins with slightly different isoelectric points (pI).

Answer 42

- Separates proteins based on their hydrophobicity. The column matrix is hydrophobic, allowing proteins to bind through hydrophobic interactions, which are enhanced in high salt concentrations. - When a protein solution with high salt is applied to the column, hydrophobic regions on the protein surface interact with the hydrophobic groups on the matrix. - Proteins are eluted by gradually decreasing the salt concentration, which weakens these hydrophobic interactions. - This method is used to purify proteins with exposed hydrophobic regions or to remove hydrophobic contaminants

Answer 43

- Separates proteins based on size using a stationary phase of porous beads. Larger molecules elute first because they cannot enter the pores, while smaller molecules elute later as they travel through the pores. - The beads contain specific-sized pores, allowing this separation. - This technique is commonly used for desalting, buffer exchange, and separating proteins with significant differences in molecular weight, as well as in the final purification steps to remove aggregates or contaminants of varying sizes.

Answer 44

- A highly specific technique that separates proteins based on their binding affinity to a ligand attached to the matrix. - The target protein binds to the ligand while other proteins are washed away. The ligand is covalently linked to the matrix in the column, allowing only the target protein to bind when the protein mixture is applied. - Other proteins are washed away, and the bound protein is eluted by adding a solution with free ligand or by altering conditions (such as pH or salt concentration) to disrupt the interaction. - This method is often used to purify proteins with specific tags (e.g., His-tagged proteins binding to nickel columns) or proteins with a natural affinity for specific molecules, like enzymes binding to substrates or inhibitors.

Answer 45

- A technique used to separate proteins based on molecular weight. Sodium dodecyl sulfate (SDS) denatures proteins and imparts a uniform negative charge, removing the influence of their native charge and shape. - Mechanism: 1. SDS Binding: SDS coats proteins with negative charges proportional to their length, causing them to unfold. 2. Gel Matrix: Proteins are loaded onto a polyacrylamide gel, where an electric current causes the negatively charged proteins to migrate towards the positive electrode. 3. Separation by Size: The gel acts as a sieve, with larger proteins moving more slowly than smaller ones. 4. Staining: After electrophoresis, proteins are visualised using dyes like Coomassie Brilliant Blue or silver stain. - Application: SDS-PAGE is widely used to estimate protein molecular weight, assess purity, and monitor protein expression in research and diagnostics.

Answer 46

- Proteins are separated based on size and charge without denaturing agents like SDS, allowing them to retain their native structure. Migration depends on their overall charge at the buffer's pH, with positively charged proteins moving towards the negative electrode (cathode) and negatively charged proteins towards the positive electrode (anode). - This method is useful for studying protein-protein interactions and enzyme activities, as the proteins maintain their functional form.

Answer 47

- Separates proteins based on their isoelectric point (pI). Proteins are applied to a gel with a pH gradient, and under an electric field, they migrate to the region where the pH matches their pI, stopping their migration. - This technique provides high-resolution separation of proteins with small pI differences and is often used in two-dimensional gel electrophoresis (2D-PAGE) for detailed protein separation by both charge (IEF) and size (SDS-PAGE)

Answer 48

- Measured in Svedbergs (S), indicates how fast a particle sediments in response to centrifugal force. It’s calculated by dividing sedimentation velocity by the applied centrifugal force. Larger, denser, and more spherical particles typically have higher sedimentation coefficients, meaning they sediment more quickly, while smaller, less dense, or elongated particles sediment more slowly.

Answer 49

Mass: Heavier particles have higher sedimentation coefficients and move faster during centrifugation. Shape: Spherical particles experience less frictional resistance and sediment faster than elongated or irregularly shaped particles of the same mass, leading to a higher s-value. Density: Denser particles sink more quickly, increasing their sedimentation coefficient

Answer 50

1. Particle _Mass_ : Larger mass increases sedimentation rate. 2. Particle _Shape_ : Spherical shapes sediment faster than elongated ones. 3. Particle _Density_ : Denser particles settle more quickly. 4. _Medium Properties_ : Denser or more viscous media slow down sedimentation. * The sedimentation coefficient is essential in ultracentrifugation for determining the size, shape, and interactions of biomolecules like proteins, ribosomes, and macromolecular complexes

Answer 51

The process of determining the amino acid sequence of a polypeptide or protein. This process typically involves a series of chemical and enzymatic steps to break down the protein into smaller fragments, identify these fragments, and then reconstruct the sequence

Answer 52

- The process involves treating the peptide with phenylisothiocyanate (PITC), which reacts with the free N-terminal amino group to form a phenylthiocarbamoyl (PTC) derivative, which is then cleaved into a cyclic phenylthiohydantoin (PTH) for identification. - This iterative process removes one amino acid at a time from the N-terminus, allowing for sequential determination of the peptide sequence. - Efficient for peptides of up to approximately 50 amino acids; for longer sequences, the protein must be fragmented and the fragments sequenced individually.

Answer 53

Can be effectively achieved through chromatography, particularly High-Performance Liquid Chromatography (HPLC), which is the most common method, and Thin-Layer Chromatography (TLC).

Answer 54

An advanced analytical technique used to identify and characterise biomolecules, particularly proteins and peptides, based on their _mass-to-charge ratio (m/z)._ Here’s how it works: 1. Ionisation * This process converts molecules in the sample into charged ions, which can be manipulated in the mass spectrometer. 2. First Mass Analysis (MS1) * The generated ions are then introduced into the first mass spectrometer (MS1), where they are separated based on their m/z ratios. 3. Fragmentation * Selected precursor ions are then fragmented in a collision cell, where they collide with neutral gas molecules. This collision causes the ions to break apart into smaller fragments, which provides structural information about the original molecules. 4. Second Mass Analysis (MS2) * The resulting fragment ions are then analysed in a second mass spectrometer (MS2). This stage measures the m/z ratios of the fragment ions, allowing for the determination of their structure and the reconstruction of the original molecule's sequence.

Answer 55

- Its linear sequence of amino acids linked by peptide bonds - The backbone conformation of a polypeptide chain is defined by the torsion angles Φ (phi) and Ψ (psi), representing rotations around the N-Cα and Cα-C bonds * These angles are limited by steric interference in the peptide backbone, constraining the protein's possible conformations * Can be visualised on a Ramachandran plot that maps the allowed Φ and Ψ values, indicating regions where alpha helices and beta sheets are likely to form.

Answer 56

The secondary structure arises from hydrogen bonding patterns between the carbonyl oxygen (C=O) and the amide hydrogen (N-H) of the polypeptide backbone. The main types of secondary structures are the alpha helix, beta strands/sheets, and PII helices.

Answer 57

A right-handed helical structure where hydrogen bonds form between the carbonyl oxygen of one residue and the amide hydrogen of another residue four positions ahead (n+4 pattern). The structure stabilises through these internal hydrogen bonds. The amino acid composition of an alpha helix is critical, with small, non-polar residues (like alanine) often promoting helix formation.

Answer 58

- Extended strands that align next to each other, forming beta sheets. - There are two types of beta sheets: parallel (where strands run in the same direction) and antiparallel (where strands run in opposite directions). * In both, hydrogen bonds form between neighbouring strands. Beta turns, common in antiparallel sheets, allow the polypeptide chain to reverse direction. Type I and II beta turns are stabilised by a hydrogen bond between the first and fourth residues, with glycine (flexible) and proline (rigid) often found in these turns.

Answer 59

- Type I beta turn, the carbonyl oxygen of the second residue points inward, while in a type II beta turn, the carbonyl oxygen points outward. Additionally, type II turns often feature glycine as the third residue to avoid steric clashes. - Only Type I β-turns are stabilized by hydrogen bonds, not Type II β-turns.

Answer 60

Refers to the three-dimensional (3D) folding of a single polypeptide chain, stabilised by various interactions like hydrophobic effects, hydrogen bonding, ionic interactions, and disulphide bonds. The folding process ensures that secondary structures (like alpha helices and beta sheets) arrange themselves to create a compact, functional protein.

Answer 61

A left-handed helical structure, prominent in proteins like collagen, where it forms a triple helix. The PII helix is stabilised by specific hydrogen bonds, and collagen's composition—rich in glycine, proline, and hydroxyproline—ensures the formation of this unique structure.

Answer 62

- Haemoglobin is a good example of tertiary and quaternary structure. Its tertiary structure shows how helices and beta sheets fold to form functional domains. In haemoglobin, each subunit contains alpha helices that come together in a compact structure to bind oxygen.

Answer 63

- The assembly of multiple polypeptide chains (subunits) into a functional complex. In proteins like haemoglobin, four subunits (two alpha and two beta chains) come together to form the functional oxygen-carrying protein. - Quaternary structure is stabilised by the same types of interactions as tertiary structure but between different polypeptide chains.

Answer 64

Pros: 1. Easy to fix the defect of the final product 2. Synthesis and assembly can be done at different locations, easy for translocation 3. Easy to maintain the genetic information 4. Easy to provide a regulatory mechanism, especially for heterocomplexes 5. Bring linked functional components into close proximity Cons: 1. The expression of different subunits has to be coordinated - both spatially and temporally

Answer 65

oligomeric

Answer 66

These are the individual polypeptide chains or subunits that constitute an oligomeric protein. Protomers can be identical (homooligomers) or different (heterooligomers), and their arrangement is fundamental to the protein’s quaternary structure. ## Footnote As an example hemoglobin consists of four protomers: two alpha subunits and two beta subunits

Answer 67

An oligomer is a protein complex composed of multiple protomers. The interactions between these subunits can result in diverse structural motifs and functional properties, enabling the protein to perform specific biological roles.

Answer 68

This symmetry type occurs when a protein can be divided into two identical halves, akin to a mirror image. It reflects the spatial arrangement of protomers such that one side is a mirror image of the other, contributing to the stability and function of the protein.

Answer 69

In proteins exhibiting rotational symmetry, the arrangement of protomers allows for a rotation around a central axis, resulting in an identical appearance after a certain angle of rotation. This symmetry is characterised by an n-fold rotational axis, where "n" denotes the number of protomers involved.

Answer 70

Helical symmetry is a specific arrangement where protomers are arranged in a helical pattern around a central axis. This results in a twisted structure that can accommodate varying lengths of the oligomer while maintaining a consistent structural motif, often observed in fibrous proteins.

Answer 71

Cyclic symmetry refers to a circular arrangement of protomers around a central axis, allowing for rotational symmetry. For example, a protein with a 6-fold cyclic symmetry has six identical subunits arranged in a ring, contributing to the formation of structures like viral capsids or symmetric enzymes.

Answer 72

- Combines both rotational and mirror symmetry. It describes arrangements where protomers are organized in such a way that there are symmetrical relationships between pairs of protomers, often resulting in more complex quaternary structures.

Answer 73

This term denotes an axis of symmetry around which a protein can be rotated by a specific angle (360°/n) to produce an identical arrangement. For instance, a 5-fold axis indicates that the structure can be rotated by 72° to achieve a congruent configuration, allowing for diverse oligomeric arrangements.

Answer 74

This specific type of n-fold axis indicates that a protein can be divided into two symmetrical halves by a 180° rotation around the axis. This symmetry is commonly found in dimeric proteins and contributes to their stability and interaction with ligands or substrates.

Answer 75

Tetrahedral symmetry describes a three-dimensional arrangement where protomers are positioned at the corners of a tetrahedron. This symmetry is characteristic of certain viral capsids and multi-subunit proteins, facilitating a stable structure that can withstand environmental stresses

Answer 76

- A type of domain motif functional bending - A beta sheet's cystines bind with the histidines of an alpha helix via a zinc bridge to form a finger looking bend between the two - This domain motif then binds to the major groove of DNA and helps regulate transcription

Answer 77

Ionic pairs in myoglobin form between oppositely charged amino acids, like lysine and glutamate/aspartate, contributing to its structural stability. These electrostatic interactions help maintain the protein's tertiary structure, particularly near the heme group or on the surface, though they are not as prevalent as in other proteins. The charged residues are well-positioned to support the formation of ionic pairs in myoglobin

Answer 78

- The study of the hydrophobic and hydrophilic properties of molecules - Quantified using a hydropathy index, which measures the relative hydrophobicity or hydrophilicity of amino acids; positive values indicate hydrophobicity, while negative values indicate hydrophilicity - Helps predict membrane-spanning regions of proteins

Answer 79

- Some proteins share similar structural features but carry out different functions - Proteins with different structures can carry out similar functions - Switching two neighbour amino acids could significantly affect its 3D-structure

Answer 80

Substances that denature proteins into random-coils by allowing water molecules to solvate nonpolar groups in the interior of proteins

Answer 81

- Described principles of denaturation and renaturation - RNase A was denatured by exposing it to a chaotropic agent, such as urea, which unfolded the protein and caused it to become denatured and "scrambled." The scrambled form of RNase A retained some structural characteristics but lacked its original enzymatic activity

Answer 82

- A denatured protein regains its native structure and function upon removal of the denaturing agent. Anfinsen found that when the chaotropic agent was removed, RNase A could refold into its native state and regain its activity, provided the conditions were suitable.

Answer 83

renaturation funnel of free energies

Answer 84

∆Gfolding=∆Hprotein-T∆Sprotein+∆Hsolvent-T∆Ssolvent

Answer 85

primary structure

Answer 86

Random coil → Form 2º structure → Stabilise 2º structure → Domain formation → Native form

Answer 87

native denatured

Answer 88

A diverse group of proteins that assist in the correct folding, assembly, and maintenance of other proteins in vivo, ensuring they achieve their functional conformations. They play a crucial role in preventing misfolding and aggregation, particularly during stressful conditions that can lead to protein denaturation.

Answer 89

These chaperones facilitate the assembly of multi-subunit protein complexes, ensuring that individual subunits are correctly incorporated into the final structure.

Answer 90

These proteins aid in the proper folding of nascent polypeptides, preventing aggregation and promoting correct conformational pathways.

Answer 91

A family of highly conserved molecular chaperones that play a crucial role in maintaining protein homeostasis, especially under conditions of cellular stress such as heat, oxidative damage, or toxic compounds.

Answer 92

Hsp40 Hsp60 Hsp70 Hsp90 Hsp100 Hsp110 Small HSPs

Answer 93

Hsp60 (Chaperonins): Hsp60 serves as a molecular folding machine, **providing a protected chamber-like structure where proteins can fold correctly without interference** from the surrounding environment. It operates as a large multimeric complex, **such as GroEL-GroES** in bacteria or mitochondrial Hsp60 in eukaryotic cells. Hsp60 is particularly important for the folding of newly synthesised mitochondrial proteins and for maintaining the stability of cytosolic proteins. Its mechanism involves **encapsulating misfolded or unfolded proteins in its cavity and utilising ATP-dependent conformational changes to facilitate proper folding**.

Answer 94

It binds to hydrophobic regions of unfolded or nascent polypeptides, **preventing their aggregation** and assisting in their proper folding. Hsp70 is also crucial for transporting proteins across membranes, such as into mitochondria or the endoplasmic reticulum, where further folding occurs. In addition to its role in folding, **Hsp70 recognises damaged proteins during stress and either refolds them or directs them to degradation pathways**, such as the proteasome or autophagy. Its activity is tightly regulated by co-chaperones like Hsp40 and nucleotide exchange factors, ensuring efficient energy utilisation during the chaperoning process.

Answer 95

Hsp90 **protects proteins from misfolding and helps maintain their functional integrity**, even under stress conditions. Its role extends to critical cellular processes such as **signal transduction, cell cycle control, and immune responses**. Clinically, Hsp90 is significant because it is **often overexpressed in cancers,** where it stabilises oncogenic proteins.

Answer 96

It **enhances the ATPase activity of Hsp70**, which is essential for the binding and release of substrate proteins during the chaperoning cycle. **Hsp40 recognises and binds unfolded or misfolded proteins, delivering them to Hsp70** for further processing and repair. In addition to its co-chaperone role, **some Hsp40 proteins directly participate in disaggregation and refolding of damaged proteins**. This makes Hsp40 essential during acute stress conditions, where it identifies destabilised proteins and ensures their stabilisation or repair

Answer 97

Hsp110 is a large chaperone protein that primarily **acts as a nucleotide exchange factor (NEF) for Hsp70**. By facilitating the exchange of ADP for ATP, Hsp110 **ensures the regeneration of the ATP-bound active form of Hsp70**, enabling it to continue its chaperoning cycle. In addition to its role as a co-chaperone, Hsp110 also **assists in protein stabilisation and refolding**, especially during severe stress.

Answer 98

Small heat shock proteins (sHSPs) function as a first line of defence against protein misfolding and aggregation. These proteins **bind to unfolded or misfolded proteins, preventing them from aggregating,** and serve as reservoirs for damaged proteins, which can later be refolded by larger chaperones like Hsp70 and Hsp100. They also play a role in **down modulating apoptosis** by interacting with apoptotic signalling pathways, often promoting cell survival under stress conditions.

Answer 99

Hsp100 (Clp), found in prokaryotes and lower eukaryotes, is part of the **Clp protease system**, which specialises in protein degradation. It uses ATPase activity to unfold damaged or misfolded proteins and translocates them to a proteolytic core like ClpP for degradation. Unlike eukaryotic Hsp110, which focuses on protein folding, Hsp110 (Clp) **ensures proteostasis by eliminating irreparably damaged proteins, with a structure tailored for degradation rather than refolding.**

Answer 100

A-4 B-3 C-6 D-1 E-5 F-2

Answer 101

Clamp-like chaperone proteins are molecular chaperones that bind to unfolded or misfolded proteins via specific regions, typically hydrophobic patches, in a manner akin to a "clamp." This binding prevents protein aggregation and assists in proper folding or transport. These chaperones are characterised by their ability to undergo conformational changes, driven by ATP binding and hydrolysis, which regulate substrate binding and release | E.g: Hsp40, Hsp90, Hsp70

Answer 102

Such as Hsp60, these proteins provide a protective environment (often in the form of a barrel-like structure) where polypeptides can fold without interference from other cellular components.

Answer 103

the spontaneous process where polypeptides fold into their native conformations without assistance from molecular chaperones. This typically occurs in proteins with simple structures that have a strong intrinsic ability to adopt their functional forms.

Answer 104

Hsp70-assisted protein folding involves Hsp70 chaperones binding to nascent or partially folded polypeptides. By stabilising exposed hydrophobic regions, Hsp70 prevents premature folding and aggregation, facilitating correct conformational development in an ATP-dependent manner.

Answer 105

This process involves both Hsp70 chaperones and chaperonins (like Hsp60). Hsp70 initially binds to nascent polypeptides to prevent aggregation and then transfers them to chaperonins, which provide a protected environment for proper folding, ensuring that proteins achieve their correct structures

Answer 106

Hsp70 proteins, such as DnaK in Escherichia coli, play a crucial role in the folding of nascent polypeptides during their synthesis on ribosomes. These chaperones specifically recognise exposed, hydrophobic regions of polypeptides, preventing nonproductive associations and ensuring the polypeptide remains unfolded until productive folding interactions can occur. Hsp70 consists of two main domains: a 44-kDa N-terminal ATP-binding domain that regulates its activity and an 18-kDa central domain that binds to hydrophobic residues. By stabilising nascent chains, Hsp70 facilitates correct folding processes critical for protein functionality, especially under stress conditions that can induce misfolding.

Answer 107

Hsp60 chaperonins Anfinsen cage

Answer 108

Within this cage, substrate polypeptides undergo forced unfolding, exposing buried hydrophobic residues, followed by folding processes that promote the correct formation of their native structure. The functioning of the GroES-GroEL complex is ATP-driven, ensuring energy is supplied for the folding process.

Answer 109

- Definition: Cellular process for assessing and managing newly synthesised proteins to ensure proper folding and functionality. - Folding on Ribosomes: Proteins begin to fold on ribosomes; some may misfold or remain partially folded. - Role of Molecular Chaperones: Chaperones like Hsp70 and chaperonins (e.g., GroEL/GroES) bind to nascent or misfolded proteins, preventing aggregation and assisting in proper folding. - Quality Control Mechanisms: Detect misfolded proteins, which may be targeted for degradation via the ubiquitin-proteasome system or redirected for refolding attempts. - Outcome of Protein Triage: Determines whether proteins achieve native conformations, are refolded, or are degraded, ensuring cellular proteostasis and function, especially under stress conditions

Answer 110

**Prions are misfolded proteins that can induce other proteins to misfold, leading to the spread of misfolding through the brain.** The primary protein involved in Alzheimer's disease is amyloid-beta. In Alzheimer's, **amyloid-beta aggregates into plaques that are toxic to brain cells.** Similarly, tau proteins also misfold and form tangles within neurons. Research has suggested that in rare cases, **misfolded tau and amyloid-beta proteins _may_ spread between individuals** in specific contexts, potentially through medical procedures or other routes.

Answer 111

represent another class of neurodegenerative diseases caused by prions, which are infectious agents composed solely of misfolded proteins. These diseases include conditions such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (mad cow disease).

Answer 112

PrPsc PrPc prion rods

Answer 113

Protein disulfide isomerase (PDI) plays a crucial role in ensuring proper protein folding by catalysing the formation and rearrangement of disulfide bonds between cysteine residues. PDI's thiol groups form mixed disulfide bonds with substrate proteins, allowing incorrect disulfide bonds to be swapped for correct ones through a process called disulfide interchange. This activity is essential for stabilising protein structure, particularly for secretory and extracellular proteins. PDI also aids in protein quality control, ensuring that misfolded proteins are corrected before they are either exported or degraded, preventing cellular dysfunction and diseases linked to misfolding

Answer 114

Intrinsically Disordered Proteins (IDPs), or Intrinsically Disordered Regions (IDRs), are protein regions that lack a stable, well-defined three-dimensional structure under physiological conditions. IDRs exhibit flexibility and randomness, adopting multiple conformations instead of folding into a single stable structure. These regions play crucial roles in cellular processes such as signal transduction, transcription regulation, and molecular recognition. IDPs are typically rich in polar, charged, and unstructured amino acids, contributing to their disordered nature.

Answer 115

A prominent example of an IDR. As a transcription factor, it regulates gene expression in response to various cellular signals, primarily through cyclic AMP (cAMP). The flexible disordered regions of CREB facilitate interactions with multiple protein partners, allowing it to dynamically modulate transcriptional activity, which is essential for processes such as neuronal plasticity, learning, and stress responses.