proteins Flashcards
(99 cards)
1
Q
what is the proteome?
A
full set of proteins encoded by the human genome – NOT the same as the number of genes.
2
Q
what are the 4 groups amino acids have?
A
hydrogen atom
α-amino group
α -carboxyl group
distinctive R group
3
Q
how many ways are there of naming an amino acid?
A
3 - full name, three letter abbreviation and 1 letter abbreviation.
4
Q
name the nonpolar amino acids
A
glycine alanine valine leucine isoleucine methionine phenylalanine tryptophan proline
5
Q
name the polar amino acids
A
serine threonine cysteine tyrosine asparagine glutamine
6
Q
name the acidic amino acids
A
aspartate
glutamate
7
Q
name the basic amino acids
A
lysine
arginine
histidine
8
Q
which form of amino acids are found in proteiins?
A
L optical isomer
9
Q
describe the primary structure of a protein.
A
the sequence of amino acids
10
Q
describe the secondary structure of a protein.
A
local spatial arrangements of amino acids in the peptide chain into pleated sheets and helices
11
Q
describe the secondary structure of a protein.
A
local spatial arrangements of amino acids in the peptide chain into pleated sheets and helices
12
Q
describe the tertiary structure of a protein.
A
organisation of the primary and secondary structures into the 3D protein shape.
13
Q
describe the quaternary structure of a protein.
A
arrangement of different subunits in a protein
14
Q
what is an amino acid in a polypeptide called?
A
a residue
15
Q
why does a polypeptide have direction?
A
because each amino acid has a N-Terminal and a C-terminal.
16
Q
which end is seen to be the start of the protein chain?
A
N-terminal
17
Q
what type of bond links amino acids?
A
covalent peptide bond
18
Q
what characteristic does a peptide bond have?
A
partial double bond - can resonate between two forms
19
Q
describe the structure of an alpha helix
A
The main chain forms the inner part of the rod, the side chains extend outwards
Hydrogen bonds between the N-H and C=O groups of the main chain stabilise the helix. These are intrachain H-bonds.
20
Q
describe the structure of an alpha helix
A
The main chain forms the inner part of the rod, the side chains extend outwards
Hydrogen bonds between the N-H and C=O groups of the main chain stabilise the helix. These are intrachain H-bonds.
21
Q
how does the helix form a rod like structure?
A
Each C=O oxygen is hydrogen bonded to the NH of the amino acid 4 residues ahead in the linear sequence.
22
Q
what are the characteristics of beta pleated sheet?
A
fully extended polypeptide chain
no elasticity
zigzag/pleated shape
R-groups lie outside the plane of the sheet
23
Q
how many different ways can beta pleated sheets form?
A
interchain
intrachain
parallel
antiparallel
24
Q
is the interior of proteins hydrophilic/phobic?
A
hydrophobic
25
give examples of proteins with quaternary structures
structural proteins (collagen monomers join together to form collagen fibres)
multi-enzyme complexes (mitochondrial ATPase)
immune system proteins (antibodies)
transport proteins (haemoglobin)
motility proteins (myosin)
26
give examples of proteins with quaternary structures
structural proteins (collagen monomers join together to form collagen fibres)
multi-enzyme complexes (mitochondrial ATPase)
immune system proteins (antibodies)
transport proteins (haemoglobin)
motility proteins (myosin)
27
list the forces that stabilise tertiary and quaternary structures
```
Electrostatic interactions
Van der Waals forces
H-bonds
Burial of hydrophobic residues
Disulphide bonds
```
28
how do disulphide bonds form?
oxidation of 2 cysteines to form cysteine
| have to be adjacent in space but not in sequence
29
what is the other name for electrostatic interactions?
salt bridges
30
what kind of molecules do Van de Waals forces occur in?
neutral molecules
31
list the three types of Van de Waals forces.
permanent dipole-permanent dipole
dipole induced dipole
London dispersion forces
32
which amino acids can form amino acids?
Most polar residues can H-bond (twelve of the amino acids).
asp, glu, lys, arg, his, tyr, ser, thr, asn, gln, trp, cys (SH).
33
which is the most important effect in stabilising proteins?
burying hydrophobic amino acids
34
how do proteins fold?
Small sequences of secondary structure form.
Stabilising forces tend to retain these
Less stable structures unravel and alternative structures form in quick succession until a more stable conformation occurs.
Folding continues in a hierarchical manner.
35
how do proteins fold?
Small sequences of secondary structure form.
Stabilising forces tend to retain these
Less stable structures unravel and alternative structures form in quick succession until a more stable conformation occurs.
Folding continues in a hierarchical manner.
36
what are the possible outcomes for a protein being incorrectly folded?
Cellular processes relying on the presence of the correct protein will not continue (e.g. phenylketonuria)
The misfolded protein may accumulate and hinder normal cellular processes (e.g. Alzheimer’s disease)
The misfolded protein may cause conformational changes in other proteins (e.g. Creutzfelt-Jacob disease)
The cell may identify the peptide for early destruction
37
what is the biochemical basis for alzheimers?
A fragment from a normal membrane protein, amyloid precursor protein, accumulates and aggregates forming insoluble fibrils of amyloid β protein in the brain.
The fibrils aggregate to form plaques.
These plaques damage and destroy neurons
38
what is the biochemical basis for Creutzfeldt Jacob Disease?
PrPSc has an identical primary sequence to a normal membrane protein PrPc but has a much higher proportion of β-pleated sheet.
Contact of normal soluble PrPc protein (mostly α-helical) with abnormal form PrPSc (mostly β-pleated sheet ) causes the PrPc protein to acquire the abnormal PrPSc structure and it accumulates
39
what are the characteristics of globular proteins?
compact, soluble – hydrophilic residues outside, hydrophobic residues hidden
40
what are the characteristics of fibrous proteins?
elongated, often have repeating amino acid sequences, insoluble due to high hydrophobic amino acid content
41
how many mutant Hbs are known?
>400
42
why do we need oxygen carrying proteins?
Cells require O2 for oxidation of foodstuffs
O2 only sparingly soluble in blood, therefore need transport and storage system.
43
what is the function of myoglobin and where is it at highest conc?
stores O2 in tissues
| highest concentration in muscle
44
what components make up a haem molecule?
porphyrin ring with Fe2+ at the centre
| Non-covalently bound in a hydrophobic crevice in protein
45
what components make up a haem molecule?
porphyrin ring with Fe2+ at the centre
| Non-covalently bound in a hydrophobic crevice in protein
46
how many ligands can Fe2+ coordinate with?
6
47
describe the binding of oxygen within myoglobin molecule
proximal histidine F8 binds to Fe directly
oxygen binds to last ligand site
changes the position of Fe
allows distal Histidine E7 to bind to oxygen as well
48
what are the advantages of the haem group being associated within a protein?
Fe atoms are kept in Fe2+ form
| Binding of other small molecules e.g. carbon monoxide is inhibited
49
what chains are found in adult Hb?
2 alpha , 2β chains
50
what does Hb being allosteric mean?
the binding of O2 to one subunit affects interactions with the other subunits
51
what is Hb dependent on?
pH and CO2 levels
52
what is Hb regulated by?
BPG
53
is O2 binding cooperative or non cooperative in Hb?
cooperative
54
does Mb or Hb have a higher affinity for oxygen?
Mb
55
why does the O2 affinity for oxygen produce a sigmoidal curve?
Binding of O2 to Hb is co-operative – binding curve is sigmoidal
Binding of one O2 makes binding of next easier
56
why does the O2 affinity for oxygen produce a sigmoidal curve?
Binding of O2 to Hb is co-operative – binding curve is sigmoidal
Binding of one O2 makes binding of next easier
57
what is the effect of one O2 binding to one Hb subunit?
proximal His F8 is pulled in
shifts helix F, EF and FG corners
altered shape transmitted to subunit surfaces
some interchain salt bridges rupture
As the subunit changes shape, it therefore changes the relationship between the 4 subunits
The β pairs slide and rotate relative to one another
58
what are the two states an Hb subunit can be in and which has a higher affinity?
T state – ‘tense state’ – more salt bridges between subunits
Low affinity for O2
R-state – ‘relaxed state’ – fewer salt bridges
High affinity for O2
59
what is the bohr effect?
lowering of pH decreases affinity of Hb for O2
60
why is the bohr effect important in the body?
Increased CO2 in blood or increased lactic acid will lower pH
Increased release of O2 to respiring rapidly tissues or muscle releasing lactic acid
61
how do H+ ions effect the binding of oxygen?
affects the protonation state of amino acid residues
additional residues are protonated – particularly histidine residues
Additional positively charged residues can form new salt bridges – these stabilise the T-state and decrease affinity for O2
62
how do H+ ions effect the binding of oxygen?
affects the protonation state of amino acid residues
additional residues are protonated – particularly histidine residues
Additional positively charged residues can form new salt bridges – these stabilise the T-state and decrease affinity for O2
63
what is BPGs effect on oxygen?
decreases affinity of Hb for O2 so causing more oxygen release in these conditions
64
where does BPG bind?
space between the β subunits – in the T-state only
65
how does BPG bind to Hb?
Negative charges on BPG interact with positive amino acid residues lining the space
66
how is foetal haemoglobin different to adult haemoglobin?
Foetal HbF 2γ2
Adult HbA 2β2
HbF binds BPG less effectively, so has higher affinity for O2
Allows efficient transfer of O2 across the placenta
67
what are the 9 critical residues of Hb?
```
F8 His Proximal His
E7 His Distal His
CD1 Phe Haem contact
F4 Leu Haem contact
B6 Gly B and E helices contact
C2 Pro Helix termination
HC2 Tyr H-bonds between H and F helices
```
68
what is conservative substitution?
maintains hydrophobic interior of molecule
| Interior of Hb often see change of one non-polar residue for another
69
what is Non-conservative substitution?
a substitution that will have a major effect on protein structure and function.
70
what is Non-conservative substitution?
a substitution that will have a major effect on protein structure and function.
71
where is collagen present and what does it form?
Major fibrous element of skin, bone, tendon, cartilage,
blood vessels, teeth
Present in most organs
Holds cells together in discrete units – basement membranes
Also a directive role in developing tissue
72
how many different types of collagen are there?
at least 12
73
what are the three categories of collagen?
fibril-forming collagens - form long fibrils
network-forming collagens - form 2-dimensional matrix – important in basal lamina
fibril-associated collagens - involved in crosslinking
74
how many chains do all collagens have?
3 protein chains
75
what is the chain composition of type 1 collagen and where is it found?
[a1(I)]2[alpha(I)] skin, tendon, bone, etc.
76
what is the chain composition of type 2 collagen and where is it found?
[alpha1(II)]3 cartilage, vitreous humor
77
what is the chain composition of type 3 collagen and where is it found?
[alpha1(III)]3 skin, muscle, often with type I
78
what is the chain composition of type 4 collagen and where is it found?
[alpha1(IV)2[alpha2(IV)] all basal lamina
79
describe the steps of collagen synthesis before secretion
Post-translational modifications
Procollagen triple helical cable (Within
fibroblasts)
80
describe the steps of collagen synthesis before secretion
Post-translational modifications
Procollagen triple helical cable (Within
fibroblasts)
81
describe the steps of collagen synthesis after secretion
```
Removal of extension peptides
Tropocollagen
Aggregation into microfibril
Cross-linking to form collagen fibre
(all in In extracellular spaces of connective tissue.)
```
82
describe the steps of collagen synthesis after secretion
```
Removal of extension peptides
Tropocollagen
Aggregation into microfibril
Cross-linking to form collagen fibre
(all in In extracellular spaces of connective tissue.)
```
83
what is the repeating sequence in collagen?
(Gly – X – Y)n
84
what are the most frequent X and Y amino acids in collagen
X often Pro
(Gly-Pro-Y)
Y often Hyp
(Gly-X-Hyp)
85
which two amino acids are hydroxilated in collagen and what is the co factor needed?
proline and lysine
| need vitamin C
86
what does hydroxyproline do?
involved in H-bond formation, which helps to stabilise the triple helix
87
what does hydroxylysine do?
attachment sites for sugar residues, and are involved in cross-linking between collagen chains
88
which direction does each polypeptide of collagen wind?
left at 3.3 residues per turn
89
which direction does each triple helix of tropocollagen wind?
right
90
which residues are on the inside and outside of a helix?
Gly on the centre, Pro and Hyp on the outside
91
how does the assembly of collagen start?
disulphide bond formation between C-terminal extensions – facilitates triple helix assembly
92
what are extension peptides
additional amino acids at each end of a chain of collagen
93
which enzyme removes the extension peptides from collagen?
Peptidase enzymes
94
how and why do cross links form in collagen?
Allysine has a reactive aldehyde group which then reacts spontaneously with the amino group on other lysine molecules, forming cross-links between adjacent chains
Covalent cross-links between and within tropocollagen molecules give strength and rigidity
95
how and why do cross links form in collagen?
Allysine has a reactive aldehyde group which then reacts spontaneously with the amino group on other lysine molecules, forming cross-links between adjacent chains
Covalent cross-links between and within tropocollagen molecules give strength and rigidity
96
why are nucleation sites important?
for calcium deposition
97
why?
just because
98
why are collegenases important?
important in tumour invasion and metastasis (spreading) – often produced at high levels by tumour cells
Dupuytren’s contracture
99
what is the cause of osteogenesis imperfect?
mutations in type 1 collagen
