Protein Folding and Function Flashcards
1
Q
What is protein structure?
A
The string of amino acids folded into a unique 3D shape
2
Q
What does protein shape depend on?
A
Amino acid sequence
3
Q
What does sequence determine?
A
Function
4
Q
What is the primary structure of a protein?
A
The linear amino acid sequence of a polypeptide chain
5
Q
What is the secondary structure of a protein?
A
The local spatial arrangement of the polypeptide backbone
6
Q
What are we looking at when considering secondary structure?
A
Localised folding, not the whole molecule
7
Q
What does secondary structure looking at the backbone mean?
A
We are not looking at side groups
8
Q
What is the tertiary structure of a protein?
A
The 3D arrangement of all atoms in a polypeptide
9
Q
What is the quaternary structure of a protein?
A
The 3D arrangement of 2+ protein sub-units
10
Q
What can you often determine from the 3D structure of a protein?
A
How it works
11
Q
When is knowing the 3D structure of a protein useful?
A
When making new drugs
12
Q
Why is knowing the 3D structure of a protein useful when making new drugs?
A
Can use it to find active site shape, and therefore make inhibitor of protein, for example if its overexpressed in a disease
13
Q
What holds together the primary structure
A
Covalent peptide bonds
14
Q
Can the bonds in a polypeptide rotate?
A
The C-N bond cannot, but other bonds can
15
Q
What does the bond angle determine?
A
The conformation of the peptide backbone, and therefore the ‘fold’ of the protein
16
Q
Why does the bond angle of the backbone determine the fold of a protein?
A
Not all bond angles are allowed, for example if there are bulky side chains the bond angles may be limited
17
Q
What do certain bond angles promote?
A
The formation of folding patterns
18
Q
How many amino acids are there in one turn of an α-helix?
A
3.6
19
Q
What is the pitch of anα-helix?
A
0.54nm
20
Q
What is meant by pitch of theα-helix?
A
How far it is for it to go one complete turn
21
Q
What kind of helix is theα-helix?
A
Right-handed
22
Q
Is theα-helix structure compact or loose?
A
Compact
23
Q
How is theα-helix held together?
A
H bonds
24
Q
Where are the H bonds between in anα-helix?
A
The backbone -C=O group of one residue is H-bonded to the -NH group 4 amino acids away
25
Where are the R groups in a α-helix?
Sit on the outside
26
Are the R groups involved in the formation of an α-helix?
No
27
Do all polypeptides form an α-helix helix structure?
No
28
What residues are strong α-helix formers?
Small, hydrophobic ones, e.g. Ala, Leu
29
What residues acts as helix breakers?
#NAME?
30
Why does Pro act as a helix breaker?
Rotation around the N-C α bond impossible
31
Why does Gly act as a helix breaker?
Has a tiny R group, so is too flexible- supports other confirmations
32
Is the ß-strand compact or extended?
Fully extended
33
How far is there between amino acids on the ß-strand?
0.35nm
34
How are the R groups positioned on the ß-strand?
Between opp sides of the chain
35
What do ß-strand’s form?
An antiparallel ß-sheet
36
How are ß-strands arranged in the antiparallel ß-sheet?
Running in opposite directions
37
What holds the ß-strands together in the ß-sheet?
Multiple interstrand H-bonds stabilise the structure
38
How does a parallel ß-sheet differ from an antiparallel one?
The H bonds are at more of an angle
39
What can secondary structures contain?
Both α-helixes and ß-strands
40
What is the tertiary structure?
The spatial arrangement of amino acids far apart in the protein sequence
41
What are the two main types of proteins?
- Globular
| - Fibrous
42
What is the role of fibrous proteins?
#NAME?
43
What is the structure of fibrous proteins?
Long strands or sheets
44
What kind of secondary structure do fibrous proteins have?
Single type of repeating secondary structure
45
Give an example of a fibrous protein?
Collagen
46
How are collagen chains arranged?
In a triple helical arrangement
47
Why are collagen molecules not α-helixes?
Because the strands are elongated collagen α-chains that form a helical structure, not one amino acid chain forming helical structure
48
What is the primary structure of collagen molecules?
Gly-X-Y repeating sequence
49
What stabilises interactions between collagen chains?
Hydrogen bonds
50
What happens to collagen in extracellular form?
The molecules line up together, forming collagen fibrils from covalently cross linked collagen molecules
51
What is collagen important for?
Structural stability in skin, bones and tendons
52
What is the role of globular proteins?
- Catalysis
| - Regulation
53
What kind of shape do globular proteins have?
Compact
54
Do all globular proteins have the same type of secondary structure?
No, variety of types
55
What features do globular proteins’ tertiary structure have?
- Motifs
| - Domains
56
What are motifs?
Folding patterns containing 1 or more elements of secondary structure
57
Give two examples of motifs
- ß-α-ß loop
| - ß-barrel
58
What are domains?
Part of a polypeptide chain that folds into a distinct shape
59
What do domains often have?
A specific functional role
60
What may a single protein have?
Lots of different domains
61
What do domains define?
The function of a protein
62
What tends to happen when different proteins have the same domain?
They do the same thing
63
How do water soluble proteins fold?
Fold so that hydrophobic side chains are buried, and polar and charged amino acids are on the surface
64
Why do water soluble fold in the way they do?
Because don’t want hydrophobic amino acids exposed to water
65
What is the folding of water soluble proteins an example of?
The characteristics of amino acids driving the 3D structure of protein
66
What do membrane proteins often show?
‘Inside out’ distribution of amino acids
67
Why is there an ‘inside out’ distribution of amino acids?
So hydrophobic amino acids can interact with the hydrophobic tails of phospholipids, and the hydrophilic exterior can form a water filled channel
68
What happens in quaternary structure?
Individually folded polypeptide chains interact with other polypeptide chains
69
What forces maintain primary structure?
Covalent
70
What forces maintain secondary structure?
H-bond
71
What forces maintain tertiary structure?
#NAME?
72
What forces maintain quaternary structure?
#NAME?
73
Where are disulphide bonds formed?
Between Cys residues
74
What is being bought together in disulphide bonds?
Sulfhydryl groups
75
What kind of reaction is the formation of disulphide bonds?
Oxidation
76
Why is the formation of disulphide bonds an oxidation reaction?
Because you loose H’s
77
How can disulphide bonds be broken?
Using reducing agents
78
What is the fate of most proteins containing disulphide bonds?
Secretion
79
Why do secreted proteins need disulphide bonds?
They need to be strong, as the environment can’t be controlled
80
What do secreted proteins need to be able to withstand?
Differences in pH, osmotic potential and concentration of various metabolites
81
Where are electrostatic interactions formed?
Between charged groups
82
Where are hydrogen bonds formed?
Between electronegative atom and a hydrogen bound to another electronegative atom
83
Are hydrophobic interactions bonds?
Not as such
84
Where does the hydrophobic effect occur?
Between hydrophobic side chains
85
What is the hydrophobic effect due to?
Displacement of water
86
How is water excluded from hydrophobic residues?
They pack together
87
Why is the exclusion of water from hydrophobic residues thermodynamically favourable?
Because if water is excluded, the entropy increases
88
What are van der Waals forces?
Dipole-dipole interactions
89
Where are van der Waals forces very important?
- In large proteins
| - When surface of two large molecules come together
90
Are proteins stable?
Not very
91
What is disruption of protein structure known as?
Denaturation
92
What is the denaturation of proteins due to?
Breaking forces that hold proteins together
93
Can denaturation break proteins down into individual amino acids?
No
94
What happens once a protein has been denatured?
It cannot do what it typically does in its native shpae
95
What factors can cause denaturing of proteins?
#NAME?
96
Why can heat denature proteins?
Because of the increased vibrational energy
97
Why can pH denature proteins?
Because it alters the ionisation states of amino acids
98
How does pH alter the ionisation states of amino acids?
It changes the [H + ], which changes interactions between charged molecules.
99
What happens to originally deprotonated groups when the pH changes?
They become protonated
100
What bonds are affected by changes in pH?
#NAME?
101
Why can detergents/organic solvents cause denaturation?
Disrupt hydrophobic interactions
102
Where is the information proteins require to fold?
In the primary structure
103
Is protein folding a random process?
No
104
How does protein folding proceed?
Through local folding
105
What do some proteins need to assist in folding?
Chaperones
106
What is the purpose of chaperones?
To stop a protein misfolding
107
How do chaperones work?
Hold on to a protein as its folding
108
What can protein misfolding cause?
Disease
109
What diseases are caused by protein misfolding?
Transmissible spongiform encephalopathies
110
Give 3 examples of transmissible spongiform encephalopathies
#NAME?
111
What has happened in transmissible spongiform encephalopathies?
Altered confirmation of normal human protein promotes the conversion of existing proteins to the diseased state
112
What are amyloidoses?
Clusters of misfolded proteins that come together
113
Give an example of a disease caused by misfolded proteins?
Alzheimers
114
How do misfolded proteins cause Alzheimers?
The proteins form plaques, which cause lesions in neuronal cells
115
What are amyloid fibres?
Misfolded, insoluble forms of a normally soluble protein
116
What is the problem with amyloid fibres?
They are highly ordered, so once formed, they are not broken down
117
What do amyloid fibres have a high degree of?
ß-sheet
118
Why are amyloid fibres so stable?
Because they have one sheet on top of another with lots of hydrophobic side chains between sheets
119
What part of the amyloid fibre forms first?
The core ß-sheet
120
Do amyloid fibres form quickly or slowly?
Slowly
121
What is the result of the slow formation of the amyloid fibres?
The diseases are usually late onset
122
How do amyloid fibres usually develop?
Starts with 1 misfolded molecule, which triggers the formation of more, which accumulate
123
How is the interchain assembly of amyloid fibres stabilised?
By hydrophobic interactions between aromatic amino acids
