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BIOC192 > Proteins > Flashcards

Proteins Flashcards

1
Q

What determines how a protein folds

A

Sequence of amino acids

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2
Q

What determines the function of a protein

A

Its structure (location of amino acid side chains)

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3
Q

What is the central dogma of molecular biology

A

DNA -> RNA -> Protein

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4
Q

What is a protein

A

Non branching polymer that form macromolecules about 50-100 A in size

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5
Q

How is protein structure determined

A

Protein crystallography, cryo-electron microscopy, NMR spectroscopy

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6
Q

How is the interior cell environment described

A

Very crowded

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7
Q

Provide examples of proteins involved in immune defence

A

HIV protease, antibodies, SARS-CoV-2

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8
Q

Provide examples of proteins involved in digestion and metabolism

A

Insulin, trypsin, amylase, alcohol dehydrogenase, hexokinase, ATP synthase

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9
Q

Provide examples of proteins involved in DNA and RNA replication

A

Primase, ligase, polymerase, etc

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10
Q

Provide examples of proteins involved in oxygen transort

A

Haemoglobin

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11
Q

What is the alpha carbon

A

Chiral carbon of amino acid

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12
Q

What is the C’ carbon

A

Carboxy carbon of amino acid

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13
Q

Which stereoisomer of amino acids is favoured

A

L (written as CORN when drawn out)

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14
Q

How are amino acids categorised

A

Non polar, polar charged (acidic: deprotonated, and basic: protonated), polar uncharged

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15
Q

What’s special about Glycine

A

Achiral, too flexible, helix breaker, common in turns

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16
Q

What’s special about Proline

A

Too rigid, helix breaker, common in turns
(Side chain binds to amino group)

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17
Q

Why are charged side chains on the exterior of proteins

A

Costs energy to bury charges, hydrophilic

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18
Q

What does E6V variant mean

A

Glutamate has been replaced by a valine at position 6 in the amino acid sequence

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19
Q

What is pKa of an ionisable group on an amino acid

A

pH at which the group is 50% ionised

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20
Q

What is the pI of an amino acid

A

The pH at which the net charge on an amino acid is 0

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21
Q

What are some examples of post translational modifications to amino acids

A

Disulfide bonds (cysteine + cysteine), phosphorylation, hydroxylation, carboxylation, metal binding, iodination, glycosylation

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22
Q

What is phosphorylation used for

A

Control enzyme activity: turn enzyme on/off, up/down

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23
Q

What is hydroxylation used for

A

Needed to prevent connective tissue diseases and scurvy, often proline and lysine involved

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24
Q

What is carboxylation used for

A

Needed for blood clotting, often glutamate involved

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25
Q

What are the 3 key features of a peptide bond

A

Planar (40% double bond character, maximises π bonding overlap, shorter than normal single bond), dipole, predominantly trans

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26
Q

What is an amino acid residue

A

An amino acid part of a polypeptide chain

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27
Q

How are amino acids numbered

A

From amino terminus to carboxy terminus

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28
Q

What is the most common variety of protein

A

One chain, globular

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29
Q

What are globular proteins mostly comprised of

A

a-helix, b-structure and turns

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30
Q

What is the primary level of protein structure

A

Amino acid sequence

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31
Q

What is the secondary level of protein structure

A

Local 3D arrangement over a short stretch of adjacent amino acid residues

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32
Q

What is the tertiary level of protein structure

A

3D structure of a complete protein chain

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33
Q

What is the quaternary level of protein structure

A

Interchain packing and structure for a protein that contains multiple protein chains

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34
Q

What is phi

A

Angle between N and alpha carbon (Memory: phi has an H, angle with N)

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35
Q

What is psi

A

Angle between C’ and alpha carbon

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36
Q

What values can phi and psi take

A

0 to +/- 180

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37
Q

What is omega

A

Angle of peptide bond: between C’ and N

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38
Q

What values can omega take

A

Very close to 0 or 180 (less free rotation due to partial double bond character)

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39
Q

When chain perfectly trans, main chain angles defined as

A

180

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40
Q

What is the limitation of phi rotation

A

O-O collision (memory: atoms involved swaps)

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41
Q

What is the limitation of psi rotation

A

NH-NH collision (memory: atoms involved swaps)

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42
Q

Why does a peptide bond prefer trans

A

Steric crowding

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43
Q

What are the features of an alpha helix

A

Right handed spiral, hydrogen bond between carbonyl O of residue n and N-H of n+4, 3.6 residues per turn, side chains point out of helix (help stabilise it), helix dipole exists (positive at N terminus) enabling ligands to bind at these locations, amino acid side chain points out every 100 degrees

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44
Q

What is a B sheet

A

More than 2 strands H bonded together (typically 2-10 per sheet), not planar: pleated with right handed twist, side chains point above and below sheet (one side polar, one non-polar), any NP-P-NP-P stretch of residues commonly forms a B strand

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45
Q

What is a B strand

A

~6-15 amino acid residues, more extended structure than helices

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46
Q

What type of H bonds do parallel beta strands have

A

Angled (memory: parallel strand = not parallel bonds)

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47
Q

What type of H bonds do anti parallel beta strands have

A

Linear (parallel)

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48
Q

How can you determine the direction of a beta strand

A

Find N atom, then alpha carbon

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49
Q

Are linear or angled H bonds stronger

A

Linear, but in reality twist of strands compensates for non linear bonds

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50
Q

What are the key properties of turns

A

Needed to form globular proteins, short, hairpin like, usually involve 3-4 residues, 30% residues are involved in turns, high gly and pro content, H bond across turn common, more than 16 types, I and II common

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51
Q

What are loops and coils

A

Extended turns, or stretches of protein structures that don’t fit any of the standard groups

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52
Q

What does ribonuclease A do

A

Digests RNA

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53
Q

What is supersecondary structure

A

Interactions of secondary structures (helices/strands connected by turns/loops/coils)

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54
Q

What is a helix-turn-helix

A

Common supersecondary structure, helices perpendicular, Ca atom binds in loop in calcium binding proteins. Also common in DNA binding proteins

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55
Q

What is a B hairpin

A

Common supersecondary structure, antiparallel B strands

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56
Q

What is a Greek key

A

Common supersecondary structure, 4 antiparallel strands. Think of a B hairpin folded in half

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57
Q

What is a strand helix strand

A

Common supersecondary structure, strands (parallel) interact by H bonds, helix can exist outside these interactions

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58
Q

What are protein domains

A

Supersecondary structure elements combined. Independently folded regions which often possess a specific function in the protein

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59
Q

What is the most important domain for protein stability

A

Hydrophobic core

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60
Q

How many domains are in a protein

A

Small proteins usually have one, larger proteins may have multiple

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61
Q

How are proteins grouped based on tertiary structure (many more than 3 we learn)

A

alpha domain family, alpha/beta family, antiparallel beta family

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62
Q

Describe the alpha domain family
(e.g four helix bundle: 3 loops connect)

A

Mostly helical, helices pack next to each other (tilting increases stability), hydrophobic side chains point in, hydrophilic chains point out

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63
Q

Describe a globin fold (member of alpha family)

A

Amphipathic helices with side chains packed closely together within a hydrophobic core. Packing can occur between non adjacent helices

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64
Q

What is an amphipathic helix

A

Half polar, half non polar helix

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65
Q

Describe the alpha/beta family

A

Mix of alpha and beta structure e.g a/B barrel (8 strand-helix-strand repeats), a/B horseshoe fold (16 strand-helix-strand repeats)

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66
Q

Describe the antiparallel B family (e.g retinal binding protein)

A

Mostly antiparallel B structure. Strands with no helices, so are antiparallel (8 strands still form a barrel), can form baskets

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67
Q

What enables a protein to fold into its correct shape (happens spontaneously)

A

Its amino acid sequence

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68
Q

Explain the Anfinsen experiment

A

Ribonuclease denatured into reduced ribonuclease, refolded with some conditions but no ribosome needed

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69
Q

Describe the sequence of events of a protein folding

A

Formation of short secondary structure segments, subdomains form, subdomains come together to form partly folded domain that can rearrange, final domain structure emerges, small conformational adjustments to give final compact native structure

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70
Q

What confers stability to a protein’s folding

A

Non covalent interactions, covalent bonds such as disulfide bonds, hydrophobic core most important

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71
Q

What are chaperones

A

Substances which assist protein folding

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72
Q

What are the three types of proteins (in terms of how they fold)

A

Chaperone independent, chaperone dependent and chaperonin-dependent

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73
Q

What is a chaperonin

A

Chamber and lid into which protein goes to be folded (e.g GroEL-GroES)

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74
Q

What is denaturation

A

Weakening of non-covalent interactions leading to unfolding and loss of biological function

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75
Q

What can cause denaturation

A

Change in pH, heat, detergents, organic solvents, urea, guanidium HCl

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76
Q

What is misfolding

A

Normally folded proteins change shape and become misfolded, can cause other proteins to change their shape as well leading to potentially disastrous consequences

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77
Q

What are Prion diseases
(prions: proteins infectious agent)
Abnormal form of prion protein, PrP induces normal form to become misfolded

A

Proteins that get misfolded then induce other proteins to misfold (a to B transformation): protein PrP changes shape then forms aggregates that cause brain damage: bovine spongiform encephalopathy (BSE), Creutzfeldt-Jacob Disease (CJD) and Kuru

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78
Q

What is the general transformation of structure in prion misfolding

A

Mostly alpha structure to mostly beta structure

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79
Q

What other diseases are thought to be partially caused by protein misfolding or aggregation

A

Alzheimer’s, Type 2 diabetes. (Prions not involved, abnormally folded amyloid thought to contribute)

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80
Q

Life can be at a steady state, but not:

A

At equilibrium (to enable useful work to be done)

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81
Q

How do enzymes catalyse thermodynamically favourable reactions

A

Lower activation energy (overall ΔG not changed) (energy required to reach transition state)

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82
Q

What are the classes of enzymes

A

Oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases

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83
Q

What do Oxidoreductases do

A

Redox reactions

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84
Q

What do transferases do

A

Transfer a functional group

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85
Q

What do hydrolases do

A

Hydrolysis reactions

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86
Q

What do lyases do

A

Non-hydrolytic breaking or making of bonds

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87
Q

What do isomerases do

A

Transfer of atoms/groups within a molecule to yield an isomeric form

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88
Q

What do ligases do

A

Join two molecules together (form a new bond: usually coupled to ATP cleavage)

89
Q

What are cofactors

A

Non protein factors to help enzymes catalyse reactions

90
Q

What are the two types of cofactors

A

Coenzymes, metal ions

91
Q

How do metal ions act as cofactors

A

Lewis acids (electron acceptors) so participate in acid-base catalysis. Form coordination compounds with precise geometries (position reactants exactly where they need to be)

92
Q

What are coenzymes

A

Small organic molecules, co-substrates, carriers (of electrons, atoms, functional groups), often derived from vitamins

93
Q

What cofactor facilitates glycogen phosphorylase activity

A

PLP (covalently linked to lysine residue: coenzymes add more diversity to amino acid residues)

94
Q

What are the key features of active sites

A

Have amino acid side chains pointing into them. Bind substrates through multiple weak interactiosn. Determine specificity of reaction

95
Q

Why are substrates bound through weak interactions

A

If really tight, hard to get speed of reaction required. Ensure specificity (weak bonds can only form if substrate is precisely positioned) and reversibility

96
Q

What does optimal binding refer to

A

Enzyme and substrate not binding too tight. E+S > ES (but can’t have too low energy or would be an inhibitor not an enzyme).

97
Q

What are the types of enzyme-substrate bond

A

Ionic bonds (make use of charged side chains, less directional than H bonds), Hydrogen bonds (directional, side chain or backbone O and N atoms can act as donors and acceptors), Van der Waals interactions (weakest, between any atoms in close proximity), Covalent bonds (rare, much stronger)

98
Q

How are active sites specific

A

Geometric and stereospecificity

99
Q

What are the two models for enzyme-substrate binding

A

Lock and key, induced fit

100
Q

What is the lock and key model

A

Substrate perfectly fits enzyme active site

101
Q

What is the induced fit model

A

Enzyme undergoes conformational change upon binding to substrate

102
Q

How is the energy of the transition state lowered

A

Transition state optimal binding: ground state destabilisation, transition state stabilisation. Provide an alternate reaction pathway with a lower energy transition state.

103
Q

How is transition state optimal binding enabled

A

By having an active site that has shape/charge complementarity to the transition state, not the substrate (enzyme binds TS more strongly than substrate)

104
Q

What are the 5 types of enzymatic catalytic mechanisms

A

Preferential binding of transition state, proximity and orientation effects, acid-base catalysis, metal ion catalysis, covalent catalysis

105
Q

What is the problem with trying to design analogues of the transition state

A

Transition state is transient and cannot be isolated

106
Q

What is an example of a transition state analogue as a drug

A

Lipitor: powerful cholesterol lowering drug

107
Q

For two molecules to react they must be

A

Close together and in the correct orientation

108
Q

What is acid base catalysis

A

The transfer of protons (often involves histadine)

109
Q

What is metal ion catalysis

A

Metal ions providing specific coordination geometries, acting as lewis acids (accept electrons to polarise water or other functional groups), sites for electron transfer (redox reactions)

110
Q

What does hexokinase use as a cofactor

A

Mg2+

111
Q

What is covalent catalysis

A

Involves the formation of a reactive, short lived intermediate which is covalently attached to the enzyme, then this attachment is hydrolysed

112
Q

What does a progress curve measure

A

The appearance of product (or disappearance of substrate) with time

113
Q

Why is it important to measure the initial velocity of a reaction

A

This is the linear portion of a progress curve, substrate becomes limiting over time / product inhibits reaction

114
Q

When does increasing the amount of enzyme increase the rate of reaction

A

When substrate is in excess

115
Q

How does reaction rate progress when there is a fixed amount of enzyme (michaelis menten)

A

Increases in a linear way initially, eventually all active sites become occupied and rate of reaction stops increasing

116
Q

How do kinetics change in the Michaelis Menten curve

A

First order kinetics during linear portion, then 0th order kinetics as rate no longer depends on substrate concentration

117
Q

What is Vmax

A

Maximum reaction velocity possible when substrate is in excess. Rectangular hyperbola: never actually reach Vmax

118
Q

What is Km

A

The substrate concentration at which V=Vmax/2. A measure of affinity

119
Q

What is the Michaelis menten equation

A

V = Vmax[S]/Km+[S]

120
Q

What is the Michaelis menten equation used for

A

To calculate velocity of a reaction at any particular substrate concentration. (Enzyme must obey Michaelis menten kinetics)

121
Q

What is the Michaelis Menten model reaction

A

E + S -> ES -> E + P
k1, k-1 k2
First arrow equilibrium

122
Q

What are the assumptions of the Michaelis Menten model

A

Product is not converted back to substrate
Rate of ES formation is equal to its breakdown (change in ES concentration over time is 0)
Measuring initial rates means substrate concentration does not change significantly (only measuring before we start running out of substrate)

123
Q

What is the lineweaver burk plot

A

1/V against 1/[S]

124
Q

What is the y intercept of a lineweaver burk

A

1/Vmax

125
Q

What is the x intercept of a lineweaver burk plot

A

-1/Km

126
Q

What is the slope of a lineweaver burk plot

A

Km/Vmax

127
Q

What is specific about Km

A

Specific to each enzyme-substrate pair (an enzyme can have multiple Km values)

128
Q

What does a low Km indicate

A

A high binding affinity

129
Q

What is the dissociation constant of an enzyme substrate pair (approximately)

A

Km = Kd = k-1 / k1
(rate of formation of ES / rate of dissociation of ES)

130
Q

Why is [S] often below Km in physiology

A

So that rate control is effective, substrate not queuing for active site

131
Q

What is kcat

A

Turnover number. Number of substrate molecules converted to product per enzyme per unit time, when E is saturated with S. Helps to define the activity of one enzyme molecule: a measure of catalytic activity (how good that enzyme is at getting from ES -> E + P)

132
Q

What is the overall measure for enzyme efficiency

A

kcat/ Km
Higher the number, greater the efficiency

133
Q

What is the upper limit for kcat/Km

A

Diffusion controlled limit, the rate at which enzyme and substrate diffuse together (~10^9s^-1M^-1)

134
Q

What are perfect enzymes

A

Enzymes with kcat/Km above 10^8s^-1M^-1

135
Q

What are the two classes of inhibitor

A

Irreversible and reversible

136
Q

What are the two types of reversible inhibitor

A

Competitive and non competitive (can be pure or mixed)

137
Q

What is an irreversible inhibitor

A

Covalently binds to enzyme (side chain in active site) and permanently inactivates it

138
Q

What is a reversible inhibitor

A

Binds to enzyme but can subsequently be released, leaving enzyme in original condition

139
Q

What is competitive inhibition

A

Either enzyme binds substrate or inhibitor (active site)

140
Q

What effect does a competitive inhibitor have on Km

A

Increases. More substrate needed to outcompete inhibitor

141
Q

What effect does a competitive inhibitor have on Vmax

A

No effect

142
Q

What effect does a non competitive inhibitor have on Km

A

No effect

143
Q

What effect does a non competitive inhibitor have on Vmax

A

Decreases. S still binds, but transition state stabilisation no longer optimal

144
Q

What is non competitive inhibition

A

Inhibitor binds at different site to substrate

145
Q

What is pure non competitive inhibition

A

Binding of I has no effect on binding of S, substrate binds to E and EI with same affinity

146
Q

What is different about mixed non competitive inhibition

A

Vmax and Km both change

147
Q

How is glycogen phosphorylase’s on/off state regulated

A

PTMs, interaction with other small molecules

148
Q

What are the two ways of glycogen phosphorylase being tuned up

A

Indicator that we need energy (AMP) promotes active state of enzyme. Or cellular signals activate phosphorylase kinase and serine phosphorylation of glycogen phosphorylase (allosteric PTM)

149
Q

What are the two ways of glycogen phosphorylase being tuned down

A

Glucose-6-P binds at an allosteric site, or caffeine/purines bind at another site. Inhibits glycogen phosphorylase activity and reduces ATP production

150
Q

What are the methods of enzyme regulation

A

Covalent modification (e.g phosphorylation), allosteric effects, proteolytic cleavage, turn gene expression on/off, degrade enzyme

151
Q

What is the purpose of myoglobin

A

Stores oxygen in muscles.

152
Q

What is the primary structure of myoglobin

A

~150 amino acids

153
Q

What is the secondary structure of myoglobin

A

8 alpha helices (A-H) + connecting loops

154
Q

What is the tertiary structure of myoglobin

A

Globin fold, hydrophobic pocket (where heme sits: interacts with HisF8)

155
Q

What is the quaternary structure of myoglobin

A

Monomer

156
Q

What is a haem group

A

Prosthetic (non protein) co factor. 4 pyrrole rings linked together in a plane. Fe in middle

157
Q

What is the Fe of a haem group bound to

A

6 coordinate bonds: 4 to N atoms of pyrrole rings, 1 to N atom of HisF8, one to oxygen

158
Q

What is the Beer Lambert Law

A

Conversion from absorbance to concentration.
Absorbance = E(Lmol^-1cm^-1) * c(molL^-1) * l (cm)

159
Q

How is spectroscopy used to measure oxygen binding

A

Globins absorb light differently depending on whether they have oxygen bound

160
Q

How does oxygen binding change haem structure

A

Brings Fe into plane

161
Q

What allows dissociation of oxygen

A

Coordination of an additional His on opposite side of haem distorts gas binding and enables reversibility

162
Q

What is the purpose of haemoglobin

A

Transport oxygen in the blood

163
Q

What is different about haemoglobin compared to myoglobin
Same: Each subunit 8 helices (A-H), connected by loops, 4 units interact non covalently

A

Tetramer, 2 slightly different subunits (2 alpha (141 amino acids), 2 beta(146 amino acids)).

164
Q

Why does myoglobin have a hyperbolic binding curve

A

Becomes saturated with oxygen at low concentrations, only releases when oxygen levels very low

165
Q

Why does haemoglobin have a sigmoidal binding curve

A

In tissues (low oxygen) will give up oxygen, only becomes saturated when partial pressure very high (lungs)

166
Q

What is cooperativity

A

One subunit affecting other subunits of haemoglobin to bind oxygen (requires oligomer: tetramer in this case)

167
Q

What is allostery in the context of globins

A

Binding to other sites: haemoglobin and myoglobin are not enzymes! (BPG, CO2)

168
Q

How does haemoglobin have a sigmoidal binding curve

A

Cooperativity and allostery

169
Q

What is the T state

A

Tense, low oxygen affinity

170
Q

What is the R state

A

Relaxed, high oxygen affinity

171
Q

What is the structure of deoxyhaemoglobin described as

A

Dished/domed haem

172
Q

What is the structure of oxyhaemoglobin described as

A

Flattened (Pulls HisF8 toward binding site) Anything that keeps HisF8 away works against oxygen binding

173
Q

What mechanisms affect balance of T and R states

A

Allosteric regulation, pH, physiological/genetic variants. All linked

174
Q

Cooperativity is prominent only in presence of allosteric inhibitors of binding. What are the inhibitors that stabilise the T state

A

BPG, CO2, H+

175
Q

How does BPG stabilise the T state

A

Allosterically binds to deoxy-Hb by electrostatic interactions. Reduces oxygen affinity. Think of BPG as a wedge between B subunits

176
Q

Why is it smart that BPG stabilises the T state

A

Because BPG is produced during respiration, so promotes oxygen release when it is needed

177
Q

How do CO2 and H+ reduce oxygen affinity

A

Bohr Effect. CO2 lowers pH which favours protonation of histadine residues, promoting ionic interactions. CO2 can bind directly to N termini of B subunit, stabilising T state. CO2 lowers oxygen affinity both directly and via lower pH of blood

178
Q

Why do foetuses have different haemoglobin structures (gamma)

A

Higher affinity for oxygen so that it crosses the placenta. Holds oxygen more tightly, less sensitive to BPG

179
Q

How does foetal haemoglobin differ structurally to normal

A

Serine residues replacing 2 histadine residues at BPG binding site

180
Q

What does the E6V variant result in

A

Sickle cell anaemia: abnormal hydrophobic reaction, particularly exposed in T state

181
Q

How is sickle cell anaemia treated

A

CRISPR: upregulate foetal haemoglobin
Voxelator: oxygen-affinity modulator (acts like BPG), stabilises oxygenated state, less in T state, less prone to polymerisation

182
Q

What are the steps in receptor activation/inhibition

A
  1. Chemical substance travels from source
  2. Interacts with target protein (binding/reception)
  3. Protein activated/inhibited
  4. Functional consequences that change cellular response
183
Q

What is an inhibitor

A

A compound that binds to an enzyme and reduces its activity

184
Q

What is a receptor

A

Cellular protein (or assembly of proteins) that control chemical signalling between and within cells

185
Q

What is different about a receptor compared to an enzyme

A

Can have several binding sites, bind ligands, release ligand unchanged

186
Q

What is similar about receptors and enzymes

A

Can be membrane bound or free in cytosol, can be activated and inhibited, used as drug targets

187
Q

What is the same about all ligands

A

All make chemical contacts with their specific receptors

188
Q

What are the types of ligands

A

Endogenous (produced in the body) and exogenous (drugs and toxins)

189
Q

Where are most receptors located

A

Outer cell membrane, sensors of extracellular environment (ligand doesn’t usually have to pass through membrane)

190
Q

What model of enzyme/substrate binding can be applied to receptors

A

Lock and key: specificity essential to function. Enough chemical reactions must exist for binding to occur

191
Q

What is an agonist

A

Chemical substance (ligand) that binds a receptor and activates it (receptor undergoes a conformational change in order to be activated)

192
Q

What is signal transduction

A

The chain of events where messages are passed on through the cell initiated by an activated receptor. Provide opportunities for coordination and regulation of the cellular response

193
Q

What is an antagonist

A

A chemical substance (ligand) which binds to a receptor and prevents activation by an agonist (signal transduction does not occur, chemical interactions not sufficient to cause conformational change)

194
Q

What receptor does adrenaline act on

A

Beta-adrenergic receptor (GPCR), signal transduction causes bronchodilation. Insulin receptor (RTK), signal transduction causes glucose uptake.

195
Q

What are the structural features of a GPCR

A

Extracellular N terminus, 3 extracellular loops, intracellular C terminus, 3 intracellular loops. 7 intramembrane alpha helices

196
Q

How can the message be passed on in signal transduction

A

Using proteins, chemical signals (second messengers), sequential phosphorylation

197
Q

What are second messengers (especially used by GPCRS)

A

Intracellular molecules that change in concentration in response to receptor activation and transmit signals from the receptor to other relay molecules because they’re not attached to the membrane.

198
Q

What are some examples of second messengers

A

cAMP, cGMP, calcium ion, diacylglycerol (DAG), inositol 1,4,5-triphosphate (IP3)

199
Q

What do phosphorylation and dephosphorylation do

A

Turn protein activity on and off or up and down as required

200
Q

What enzyme transfers phosphate groups from ATP to proteins

A

Kinases

201
Q

What enzyme removes phosphate groups from proteins to control signal transduction

A

Phosphatases

202
Q

What are the 3 ways signal transduction is regulated (stopped)

A

Ligand dissociation, internalisation (endocytosis), phosphotases

203
Q

What does Gαs (stimulatory G protein) do

A

Activates enzyme called adenylate cyclase

204
Q

What does Gαi (inhibitory G protein) do

A

Decreases activity of adenylate cyclase

205
Q

What is adenylate cyclase

A

Membrane bound enzyme (looks like 2 GPCRS joint together intracellularly)

206
Q

What is the process of a Gαs protein coupled GPCR upon activation

A

Gαs is activated leading to activation of adenylate cyclase which increases activity of cAMP, which increases activity of protein kinase A, which results in further signal transduction leading to cell response

207
Q

What does the activation of a GPCR in a liver cell result in

A

Glycogen breakdown and lipolysis

208
Q

What type of ligand are glucagon and insulin

A

Peptide ligands

209
Q

What does the activation of GLP-1 GPCR on beta cells by GLP-1 (produced in pancreas) result in

A

Insulin secretion

210
Q

What signal transduction mechanism do RTKs use

A

Phosphorylation of adaptor proteins

211
Q

What is the process of signal transduction as a ligand binds an RTK

A

Agonist ligand binds, receptor changes conformation and becomes activated, receptor autophosphorylation occurs, adaptor protein is phosphorylated

212
Q

What type of receptor are insulin receptors

A

RTK

213
Q

What is the process of signal transduction as insulin binds insulin RTK in muscle and fat

A

Receptor activation causes phosphorylation of adaptor protein, further transduction events, GLUT-4 translocation into membrane by exocytosis, glucose enters cell (blood glucose lowered)

214
Q

What is the process of signal transduction as insulin binds insulin RTK in the liver

A

Receptor activation causes phosphorylation of adaptor protein and further signal transduction events, leading to glycogen synthesis

215
Q

What is the signal transduction process for ligand gated ion channels

A

Agonist binds causing conformational change, ions flow directly through channel to produce effects. Fastest signalling

216
Q

How can the same ligand/receptor pairing have different effects in different cells

A

Because they use different combinations of relay molecules for signal transduction

217
Q

What further enables cells to coordinate signals from incoming ligands

A

Cross talk (interaction of different pathways) and pathway branching (original pathway branching into different ones)

218
Q

What are the structural features of a G protein (guanine nucleotide binding protein)

A

Heterotrimeric (3 different subunits): alpha, beta, gamma. Different types of alpha subunits with opposing effects

219
Q

Why does autophosphorylation of RTKs occur

A

Kinase intrinsic in its structure

BIOC192 (3 decks)

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