Proteins Flashcards
1
Q
What determines how a protein folds
A
Sequence of amino acids
2
Q
What determines the function of a protein
A
Its structure (location of amino acid side chains)
3
Q
What is the central dogma of molecular biology
A
DNA -> RNA -> Protein
4
Q
What is a protein
A
Non branching polymer that form macromolecules about 50-100 A in size
5
Q
How is protein structure determined
A
Protein crystallography, cryo-electron microscopy, NMR spectroscopy
6
Q
How is the interior cell environment described
A
Very crowded
7
Q
Provide examples of proteins involved in immune defence
A
HIV protease, antibodies, SARS-CoV-2
8
Q
Provide examples of proteins involved in digestion and metabolism
A
Insulin, trypsin, amylase, alcohol dehydrogenase, hexokinase, ATP synthase
9
Q
Provide examples of proteins involved in DNA and RNA replication
A
Primase, ligase, polymerase, etc
10
Q
Provide examples of proteins involved in oxygen transort
A
Haemoglobin
11
Q
What is the alpha carbon
A
Chiral carbon of amino acid
12
Q
What is the C’ carbon
A
Carboxy carbon of amino acid
13
Q
Which stereoisomer of amino acids is favoured
A
L (written as CORN when drawn out)
14
Q
How are amino acids categorised
A
Non polar, polar charged (acidic: deprotonated, and basic: protonated), polar uncharged
15
Q
What’s special about Glycine
A
Achiral, too flexible, helix breaker, common in turns
16
Q
What’s special about Proline
A
Too rigid, helix breaker, common in turns
(Side chain binds to amino group)
17
Q
Why are charged side chains on the exterior of proteins
A
Costs energy to bury charges, hydrophilic
18
Q
What does E6V variant mean
A
Glutamate has been replaced by a valine at position 6 in the amino acid sequence
19
Q
What is pKa of an ionisable group on an amino acid
A
pH at which the group is 50% ionised
20
Q
What is the pI of an amino acid
A
The pH at which the net charge on an amino acid is 0
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
22
Q
What is phosphorylation used for
A
Control enzyme activity: turn enzyme on/off, up/down
23
Q
What is hydroxylation used for
A
Needed to prevent connective tissue diseases and scurvy, often proline and lysine involved
24
Q
What is carboxylation used for
A
Needed for blood clotting, often glutamate involved
25
What are the 3 key features of a peptide bond
Planar (40% double bond character, maximises π bonding overlap, shorter than normal single bond), dipole, predominantly trans
26
What is an amino acid residue
An amino acid part of a polypeptide chain
27
How are amino acids numbered
From amino terminus to carboxy terminus
28
What is the most common variety of protein
One chain, globular
29
What are globular proteins mostly comprised of
a-helix, b-structure and turns
30
What is the primary level of protein structure
Amino acid sequence
31
What is the secondary level of protein structure
Local 3D arrangement over a short stretch of adjacent amino acid residues
32
What is the tertiary level of protein structure
3D structure of a complete protein chain
33
What is the quaternary level of protein structure
Interchain packing and structure for a protein that contains multiple protein chains
34
What is phi
Angle between N and alpha carbon (Memory: phi has an H, angle with N)
35
What is psi
Angle between C' and alpha carbon
36
What values can phi and psi take
0 to +/- 180
37
What is omega
Angle of peptide bond: between C' and N
38
What values can omega take
Very close to 0 or 180 (less free rotation due to partial double bond character)
39
When chain perfectly trans, main chain angles defined as
180
40
What is the limitation of phi rotation
O-O collision (memory: atoms involved swaps)
41
What is the limitation of psi rotation
NH-NH collision (memory: atoms involved swaps)
42
Why does a peptide bond prefer trans
Steric crowding
43
What are the features of an alpha helix
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
44
What is a B sheet
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
45
What is a B strand
~6-15 amino acid residues, more extended structure than helices
46
What type of H bonds do parallel beta strands have
Angled (memory: parallel strand = not parallel bonds)
47
What type of H bonds do anti parallel beta strands have
Linear (parallel)
48
How can you determine the direction of a beta strand
Find N atom, then alpha carbon
49
Are linear or angled H bonds stronger
Linear, but in reality twist of strands compensates for non linear bonds
50
What are the key properties of turns
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
51
What are loops and coils
Extended turns, or stretches of protein structures that don't fit any of the standard groups
52
What does ribonuclease A do
Digests RNA
53
What is supersecondary structure
Interactions of secondary structures (helices/strands connected by turns/loops/coils)
54
What is a helix-turn-helix
Common supersecondary structure, helices perpendicular, Ca atom binds in loop in calcium binding proteins. Also common in DNA binding proteins
55
What is a B hairpin
Common supersecondary structure, antiparallel B strands
56
What is a Greek key
Common supersecondary structure, 4 antiparallel strands. Think of a B hairpin folded in half
57
What is a strand helix strand
Common supersecondary structure, strands (parallel) interact by H bonds, helix can exist outside these interactions
58
What are protein domains
Supersecondary structure elements combined. Independently folded regions which often possess a specific function in the protein
59
What is the most important domain for protein stability
Hydrophobic core
60
How many domains are in a protein
Small proteins usually have one, larger proteins may have multiple
61
How are proteins grouped based on tertiary structure (many more than 3 we learn)
alpha domain family, alpha/beta family, antiparallel beta family
62
Describe the alpha domain family
(e.g four helix bundle: 3 loops connect)
Mostly helical, helices pack next to each other (tilting increases stability), hydrophobic side chains point in, hydrophilic chains point out
63
Describe a globin fold (member of alpha family)
Amphipathic helices with side chains packed closely together within a hydrophobic core. Packing can occur between non adjacent helices
64
What is an amphipathic helix
Half polar, half non polar helix
65
Describe the alpha/beta family
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)
66
Describe the antiparallel B family (e.g retinal binding protein)
Mostly antiparallel B structure. Strands with no helices, so are antiparallel (8 strands still form a barrel), can form baskets
67
What enables a protein to fold into its correct shape (happens spontaneously)
Its amino acid sequence
68
Explain the Anfinsen experiment
Ribonuclease denatured into reduced ribonuclease, refolded with some conditions but no ribosome needed
69
Describe the sequence of events of a protein folding
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
70
What confers stability to a protein's folding
Non covalent interactions, covalent bonds such as disulfide bonds, hydrophobic core most important
71
What are chaperones
Substances which assist protein folding
72
What are the three types of proteins (in terms of how they fold)
Chaperone independent, chaperone dependent and chaperonin-dependent
73
What is a chaperonin
Chamber and lid into which protein goes to be folded (e.g GroEL-GroES)
74
What is denaturation
Weakening of non-covalent interactions leading to unfolding and loss of biological function
75
What can cause denaturation
Change in pH, heat, detergents, organic solvents, urea, guanidium HCl
76
What is misfolding
Normally folded proteins change shape and become misfolded, can cause other proteins to change their shape as well leading to potentially disastrous consequences
77
What are Prion diseases
(prions: proteins infectious agent)
Abnormal form of prion protein, PrP induces normal form to become misfolded
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
78
What is the general transformation of structure in prion misfolding
Mostly alpha structure to mostly beta structure
79
What other diseases are thought to be partially caused by protein misfolding or aggregation
Alzheimer's, Type 2 diabetes. (Prions not involved, abnormally folded amyloid thought to contribute)
80
Life can be at a steady state, but not:
At equilibrium (to enable useful work to be done)
81
How do enzymes catalyse thermodynamically favourable reactions
Lower activation energy (overall ΔG not changed) (energy required to reach transition state)
82
What are the classes of enzymes
Oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases
83
What do Oxidoreductases do
Redox reactions
84
What do transferases do
Transfer a functional group
85
What do hydrolases do
Hydrolysis reactions
86
What do lyases do
Non-hydrolytic breaking or making of bonds
87
What do isomerases do
Transfer of atoms/groups within a molecule to yield an isomeric form
88
What do ligases do
Join two molecules together (form a new bond: usually coupled to ATP cleavage)
89
What are cofactors
Non protein factors to help enzymes catalyse reactions
90
What are the two types of cofactors
Coenzymes, metal ions
91
How do metal ions act as cofactors
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
What are coenzymes
Small organic molecules, co-substrates, carriers (of electrons, atoms, functional groups), often derived from vitamins
93
What cofactor facilitates glycogen phosphorylase activity
PLP (covalently linked to lysine residue: coenzymes add more diversity to amino acid residues)
94
What are the key features of active sites
Have amino acid side chains pointing into them. Bind substrates through multiple weak interactiosn. Determine specificity of reaction
95
Why are substrates bound through weak interactions
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
What does optimal binding refer to
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
What are the types of enzyme-substrate bond
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
How are active sites specific
Geometric and stereospecificity
99
What are the two models for enzyme-substrate binding
Lock and key, induced fit
100
What is the lock and key model
Substrate perfectly fits enzyme active site
101
What is the induced fit model
Enzyme undergoes conformational change upon binding to substrate
102
How is the energy of the transition state lowered
Transition state optimal binding: ground state destabilisation, transition state stabilisation. Provide an alternate reaction pathway with a lower energy transition state.
103
How is transition state optimal binding enabled
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
What are the 5 types of enzymatic catalytic mechanisms
Preferential binding of transition state, proximity and orientation effects, acid-base catalysis, metal ion catalysis, covalent catalysis
105
What is the problem with trying to design analogues of the transition state
Transition state is transient and cannot be isolated
106
What is an example of a transition state analogue as a drug
Lipitor: powerful cholesterol lowering drug
107
For two molecules to react they must be
Close together and in the correct orientation
108
What is acid base catalysis
The transfer of protons (often involves histadine)
109
What is metal ion catalysis
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
What does hexokinase use as a cofactor
Mg2+
111
What is covalent catalysis
Involves the formation of a reactive, short lived intermediate which is covalently attached to the enzyme, then this attachment is hydrolysed
112
What does a progress curve measure
The appearance of product (or disappearance of substrate) with time
113
Why is it important to measure the initial velocity of a reaction
This is the linear portion of a progress curve, substrate becomes limiting over time / product inhibits reaction
114
When does increasing the amount of enzyme increase the rate of reaction
When substrate is in excess
115
How does reaction rate progress when there is a fixed amount of enzyme (michaelis menten)
Increases in a linear way initially, eventually all active sites become occupied and rate of reaction stops increasing
116
How do kinetics change in the Michaelis Menten curve
First order kinetics during linear portion, then 0th order kinetics as rate no longer depends on substrate concentration
117
What is Vmax
Maximum reaction velocity possible when substrate is in excess. Rectangular hyperbola: never actually reach Vmax
118
What is Km
The substrate concentration at which V=Vmax/2. A measure of affinity
119
What is the Michaelis menten equation
V = Vmax[S]/Km+[S]
120
What is the Michaelis menten equation used for
To calculate velocity of a reaction at any particular substrate concentration. (Enzyme must obey Michaelis menten kinetics)
121
What is the Michaelis Menten model reaction
E + S -> ES -> E + P
k1, k-1 k2
First arrow equilibrium
122
What are the assumptions of the Michaelis Menten model
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
What is the lineweaver burk plot
1/V against 1/[S]
124
What is the y intercept of a lineweaver burk
1/Vmax
125
What is the x intercept of a lineweaver burk plot
-1/Km
126
What is the slope of a lineweaver burk plot
Km/Vmax
127
What is specific about Km
Specific to each enzyme-substrate pair (an enzyme can have multiple Km values)
128
What does a low Km indicate
A high binding affinity
129
What is the dissociation constant of an enzyme substrate pair (approximately)
Km = Kd = k-1 / k1
(rate of formation of ES / rate of dissociation of ES)
130
Why is [S] often below Km in physiology
So that rate control is effective, substrate not queuing for active site
131
What is kcat
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
What is the overall measure for enzyme efficiency
kcat/ Km
Higher the number, greater the efficiency
133
What is the upper limit for kcat/Km
Diffusion controlled limit, the rate at which enzyme and substrate diffuse together (~10^9s^-1M^-1)
134
What are perfect enzymes
Enzymes with kcat/Km above 10^8s^-1M^-1
135
What are the two classes of inhibitor
Irreversible and reversible
136
What are the two types of reversible inhibitor
Competitive and non competitive (can be pure or mixed)
137
What is an irreversible inhibitor
Covalently binds to enzyme (side chain in active site) and permanently inactivates it
138
What is a reversible inhibitor
Binds to enzyme but can subsequently be released, leaving enzyme in original condition
139
What is competitive inhibition
Either enzyme binds substrate or inhibitor (active site)
140
What effect does a competitive inhibitor have on Km
Increases. More substrate needed to outcompete inhibitor
141
What effect does a competitive inhibitor have on Vmax
No effect
142
What effect does a non competitive inhibitor have on Km
No effect
143
What effect does a non competitive inhibitor have on Vmax
Decreases. S still binds, but transition state stabilisation no longer optimal
144
What is non competitive inhibition
Inhibitor binds at different site to substrate
145
What is pure non competitive inhibition
Binding of I has no effect on binding of S, substrate binds to E and EI with same affinity
146
What is different about mixed non competitive inhibition
Vmax and Km both change
147
How is glycogen phosphorylase's on/off state regulated
PTMs, interaction with other small molecules
148
What are the two ways of glycogen phosphorylase being tuned up
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
What are the two ways of glycogen phosphorylase being tuned down
Glucose-6-P binds at an allosteric site, or caffeine/purines bind at another site. Inhibits glycogen phosphorylase activity and reduces ATP production
150
What are the methods of enzyme regulation
Covalent modification (e.g phosphorylation), allosteric effects, proteolytic cleavage, turn gene expression on/off, degrade enzyme
151
What is the purpose of myoglobin
Stores oxygen in muscles.
152
What is the primary structure of myoglobin
~150 amino acids
153
What is the secondary structure of myoglobin
8 alpha helices (A-H) + connecting loops
154
What is the tertiary structure of myoglobin
Globin fold, hydrophobic pocket (where heme sits: interacts with HisF8)
155
What is the quaternary structure of myoglobin
Monomer
156
What is a haem group
Prosthetic (non protein) co factor. 4 pyrrole rings linked together in a plane. Fe in middle
157
What is the Fe of a haem group bound to
6 coordinate bonds: 4 to N atoms of pyrrole rings, 1 to N atom of HisF8, one to oxygen
158
What is the Beer Lambert Law
Conversion from absorbance to concentration.
Absorbance = E(Lmol^-1cm^-1) * c(molL^-1) * l (cm)
159
How is spectroscopy used to measure oxygen binding
Globins absorb light differently depending on whether they have oxygen bound
160
How does oxygen binding change haem structure
Brings Fe into plane
161
What allows dissociation of oxygen
Coordination of an additional His on opposite side of haem distorts gas binding and enables reversibility
162
What is the purpose of haemoglobin
Transport oxygen in the blood
163
What is different about haemoglobin compared to myoglobin
Same: Each subunit 8 helices (A-H), connected by loops, 4 units interact non covalently
Tetramer, 2 slightly different subunits (2 alpha (141 amino acids), 2 beta(146 amino acids)).
164
Why does myoglobin have a hyperbolic binding curve
Becomes saturated with oxygen at low concentrations, only releases when oxygen levels very low
165
Why does haemoglobin have a sigmoidal binding curve
In tissues (low oxygen) will give up oxygen, only becomes saturated when partial pressure very high (lungs)
166
What is cooperativity
One subunit affecting other subunits of haemoglobin to bind oxygen (requires oligomer: tetramer in this case)
167
What is allostery in the context of globins
Binding to other sites: haemoglobin and myoglobin are not enzymes! (BPG, CO2)
168
How does haemoglobin have a sigmoidal binding curve
Cooperativity and allostery
169
What is the T state
Tense, low oxygen affinity
170
What is the R state
Relaxed, high oxygen affinity
171
What is the structure of deoxyhaemoglobin described as
Dished/domed haem
172
What is the structure of oxyhaemoglobin described as
Flattened (Pulls HisF8 toward binding site) Anything that keeps HisF8 away works against oxygen binding
173
What mechanisms affect balance of T and R states
Allosteric regulation, pH, physiological/genetic variants. All linked
174
Cooperativity is prominent only in presence of allosteric inhibitors of binding. What are the inhibitors that stabilise the T state
BPG, CO2, H+
175
How does BPG stabilise the T state
Allosterically binds to deoxy-Hb by electrostatic interactions. Reduces oxygen affinity. Think of BPG as a wedge between B subunits
176
Why is it smart that BPG stabilises the T state
Because BPG is produced during respiration, so promotes oxygen release when it is needed
177
How do CO2 and H+ reduce oxygen affinity
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
Why do foetuses have different haemoglobin structures (gamma)
Higher affinity for oxygen so that it crosses the placenta. Holds oxygen more tightly, less sensitive to BPG
179
How does foetal haemoglobin differ structurally to normal
Serine residues replacing 2 histadine residues at BPG binding site
180
What does the E6V variant result in
Sickle cell anaemia: abnormal hydrophobic reaction, particularly exposed in T state
181
How is sickle cell anaemia treated
CRISPR: upregulate foetal haemoglobin
Voxelator: oxygen-affinity modulator (acts like BPG), stabilises oxygenated state, less in T state, less prone to polymerisation
182
What are the steps in receptor activation/inhibition
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
What is an inhibitor
A compound that binds to an enzyme and reduces its activity
184
What is a receptor
Cellular protein (or assembly of proteins) that control chemical signalling between and within cells
185
What is different about a receptor compared to an enzyme
Can have several binding sites, bind ligands, release ligand unchanged
186
What is similar about receptors and enzymes
Can be membrane bound or free in cytosol, can be activated and inhibited, used as drug targets
187
What is the same about all ligands
All make chemical contacts with their specific receptors
188
What are the types of ligands
Endogenous (produced in the body) and exogenous (drugs and toxins)
189
Where are most receptors located
Outer cell membrane, sensors of extracellular environment (ligand doesn't usually have to pass through membrane)
190
What model of enzyme/substrate binding can be applied to receptors
Lock and key: specificity essential to function. Enough chemical reactions must exist for binding to occur
191
What is an agonist
Chemical substance (ligand) that binds a receptor and activates it (receptor undergoes a conformational change in order to be activated)
192
What is signal transduction
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
What is an antagonist
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
What receptor does adrenaline act on
Beta-adrenergic receptor (GPCR), signal transduction causes bronchodilation. Insulin receptor (RTK), signal transduction causes glucose uptake.
195
What are the structural features of a GPCR
Extracellular N terminus, 3 extracellular loops, intracellular C terminus, 3 intracellular loops. 7 intramembrane alpha helices
196
How can the message be passed on in signal transduction
Using proteins, chemical signals (second messengers), sequential phosphorylation
197
What are second messengers (especially used by GPCRS)
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
What are some examples of second messengers
cAMP, cGMP, calcium ion, diacylglycerol (DAG), inositol 1,4,5-triphosphate (IP3)
199
What do phosphorylation and dephosphorylation do
Turn protein activity on and off or up and down as required
200
What enzyme transfers phosphate groups from ATP to proteins
Kinases
201
What enzyme removes phosphate groups from proteins to control signal transduction
Phosphatases
202
What are the 3 ways signal transduction is regulated (stopped)
Ligand dissociation, internalisation (endocytosis), phosphotases
203
What does Gαs (stimulatory G protein) do
Activates enzyme called adenylate cyclase
204
What does Gαi (inhibitory G protein) do
Decreases activity of adenylate cyclase
205
What is adenylate cyclase
Membrane bound enzyme (looks like 2 GPCRS joint together intracellularly)
206
What is the process of a Gαs protein coupled GPCR upon activation
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
What does the activation of a GPCR in a liver cell result in
Glycogen breakdown and lipolysis
208
What type of ligand are glucagon and insulin
Peptide ligands
209
What does the activation of GLP-1 GPCR on beta cells by GLP-1 (produced in pancreas) result in
Insulin secretion
210
What signal transduction mechanism do RTKs use
Phosphorylation of adaptor proteins
211
What is the process of signal transduction as a ligand binds an RTK
Agonist ligand binds, receptor changes conformation and becomes activated, receptor autophosphorylation occurs, adaptor protein is phosphorylated
212
What type of receptor are insulin receptors
RTK
213
What is the process of signal transduction as insulin binds insulin RTK in muscle and fat
Receptor activation causes phosphorylation of adaptor protein, further transduction events, GLUT-4 translocation into membrane by exocytosis, glucose enters cell (blood glucose lowered)
214
What is the process of signal transduction as insulin binds insulin RTK in the liver
Receptor activation causes phosphorylation of adaptor protein and further signal transduction events, leading to glycogen synthesis
215
What is the signal transduction process for ligand gated ion channels
Agonist binds causing conformational change, ions flow directly through channel to produce effects. Fastest signalling
216
How can the same ligand/receptor pairing have different effects in different cells
Because they use different combinations of relay molecules for signal transduction
217
What further enables cells to coordinate signals from incoming ligands
Cross talk (interaction of different pathways) and pathway branching (original pathway branching into different ones)
218
What are the structural features of a G protein (guanine nucleotide binding protein)
Heterotrimeric (3 different subunits): alpha, beta, gamma. Different types of alpha subunits with opposing effects
219
Why does autophosphorylation of RTKs occur
Kinase intrinsic in its structure
