Protein Folds Flashcards
1
Q
What can proteomics tell us?
A
What genes actually do
2
Q
How many proteins can 25,000 genes generate in humans?
A
Up to 100,000 proteins.
3
Q
What are some examples of post-translational modifications?
A
- Proteolytic cleavage
- Glycosylation
- Phosphorylation
4
Q
What does the function of a protein depend on?
A
Its 3D structure.
5
Q
What specifies the amino acid sequence of a protein?
A
The genetic code.
6
Q
Fill in the blank: Amino acid 🡪 _______ 🡪 Function.
A
[3D structure]
7
Q
What methods can be used to view protein structures?
A
- X-ray crystallography
- NMR
- SAXs
- Cryo-EM
- Alphafold
8
Q
Why is it important to study protein structure?
A
To understand biological reactions, design drugs, and develop pesticides and herbicides.
9
Q
How can structural data assist in protein research?
A
It can help with sequence comparison and finding related proteins.
Sequence and structural motifs can identify proteins with similar biochemical functions.
10
Q
What are the four levels of protein structure?
A
- Primary
- Secondary
- Tertiary
- Quaternary
11
Q
What does primary structure refer to?
A
Amino acid sequence.
12
Q
What is the characteristic of proline in protein structure?
A
Proline cannot be in a helix due to its ring causing a kink.
13
Q
What is the role of glycine in protein structure?
A
Glycine is very flexible and can disrupt secondary structures.
14
Q
Which amino acid is useful for determining protein concentration?
A
Tyrosine.
15
Q
What type of bonds can cysteines form?
A
Disulfide bridges.
16
Q
True or False: Histidine often interacts with metals.
A
True.
17
Q
Which amino acids bind metals?
A
C, H, D and E
18
Q
Fill in the blank: Peptides form with the release of a _______.
A
Water molecule
19
Q
What does the Ramachandran plot show?
A
The preferred conformation of the phi and psi angles.
20
Q
What is the typical conformation of amino acids?
A
Generally trans, with Calpha atoms facing away from each other.
Prolines however are usually cis and require a chaperone protein to become oriented.
21
Q
What is the structure of the alpha helix?
A
3.6 residues per turn, 13 atoms per turn.
22
Q
Strand directions in beta sheets
A
In antiparallel sheets, strands run in opposite directions.
23
Q
What types of tight turns are there in protein structure?
A
- Beta-hairpin turns I and II.
24
Q
What leads to the tertiary structure of proteins?
A
The arrangement of secondary structures.
25
What might cause a bend in a beta sheet?
A mix of both parallel and antiparal
26
What is fold space?
Tertiary structure of proteins
27
Why are there a limited number of protein folds?
Different stereochemical constraints limit the ways a sequence can fold
E.g: Ramachandran plots
28
What is AlphaFold?
A deep learning algorithm to predict protein structures from amino acid sequences
29
What impact has AlphaFold had on drug discovery?
Accelerated drug discovery for diseases like Chagas disease and leishmaniasis
30
What are structural motifs?
Smaller elements of a protein structural fold
31
List examples of structural motifs.
* Helix-turn-helix
* EF-hand
* β-hairpin
* Greek key
* β−α−β
32
Describe the helix-turn-helix motif.
* A helix followed by a turn and another helix
* Can be recognized in their sequences
* Binds Ca2+ in the turn
33
What is a β-hairpin?
Links together β-sheets and always has a glycine
34
Types of beta hairpin turns
Type 1 has a glycine in residue 2
Type 2 has a glycine as residue 1
35
What characterizes the Greek key motif?
* Antiparallel β strand with a tight turn and a wrap around.
* Can have multiple next to each other
* Cannot be recognized from sequences alone
36
What is an immunoglobulin domain?
Two greek keys "stuck on top" of each other
37
What does the β−α−β motif consist of?
A strand followed by a helix and then by another strand
38
What are the structural classifications of proteins?
* Class
* Architecture
* Topology
* Homology
39
What defines an Alpha classification in protein structure?
Mostly helices
40
What defines a Beta classification in protein structure?
Mostly strands
41
What is the TIM barrel?
A topology characterized by lots of β−α−β
42
What is the significance of IDs in protein classification?
Useful in determining whether a protein is an enzyme
43
Provide an example of a protein and its classification from SCOP.
Hemoglobin, alpha-chain from Human (Homo sapiens)
44
What is the fold of Hemoglobin according to SCOP?
Globin-like core with 6 helices
45
What is the superfamily classification of Hemoglobin?
Globin-like
46
Fill in the blank: A motif is a smaller element of a protein structural _______.
fold
47
True or False: All protein folds can be predicted from their sequences.
False
48
Beta-domain structures
* β-barrel
* Jelly Roll
* β-propellor
* Immunoglobulin fold
49
What is a β-barrel?
A tube of beta sheets with gaps between the sheets, always having an even number of strands
## Footnote
The first and last strand are often close together, and it can contain a molecule within the barrel.
50
What are the characteristics of β-barrels?
Often feature alternating hydrophobic amino acids, contain 8 stranded up-and-down barrels, and amino acids in sheets alternate between facing in and out
## Footnote
Example: Plasma-borne retinol-binding protein.
51
What is the structure of PorA from Neisseria meningitidis?
Has 16 up-and-down beta strands
## Footnote
It features shorter beta turns on the inside and longer loops on the outside.
52
What is a jelly roll in protein structure?
Characterized by beta strands separated by long non-stranded sections, with loops wrapping over and under the barrel
## Footnote
Example: Influenza virus hemagglutinin.
53
What is the significance of the β-propellor structure?
Rich in tryptophan and aspartase, made of 7 repeats of propellor forming a circular structure
## Footnote
Influenza virus neuraminidase contains 6 repeats of the propeller section.
54
What is an immunoglobulin fold?
Composed of two Greek key motifs sandwiched on top of each other, connected by a disulphide bond bridge
## Footnote
Examples include immunoglobulins (antibodies) and T cell receptors.
55
True or False: β-barrels always contain an odd number of strands.
False
## Footnote
They always have an even number of strands.
56
Fill in the blank: The immunoglobulin fold looks like a beta barrel but _______.
[isn't]
## Footnote
The topology is similar to that of jelly rolls, but the pattern is distinct.
57
What is a key feature of the jelly roll structure?
Loops wrap over and under the barrel
## Footnote
This structure is quite common in various proteins.
58
What types of proteins commonly exhibit the β-propellor structure?
Proteins rich in tryptophan and aspartase
## Footnote
This structure also allows for flexibility in the number of 'blades'.
59
What are the key structures of beta-domain proteins?
β-barrel, Jelly roll, β-propellor, Immunoglobulin fold
## Footnote
These structures are essential in various protein functions.
60
What are tandem repeats in protein structures?
Folds with tandem repeats of specific structural repeats, often called solenoid proteins
## Footnote
They include β-solenoid, proline-rich repeats stabilized by proline stacking.
61
What characterizes alpha beta-domain structures?
Based on repeats of the β-α-β motif and are all right-handed
## Footnote
These are the most common protein structures.
62
What is a TIM barrel?
An alpha/beta barrel with a topology limited to 8 strands and helices
## Footnote
It likely functions as an enzyme.
63
What is the topology of an alpha/beta barrel?
Single sheet direction, known as a 'singly wound' fold
## Footnote
All arrows in the structure point towards the active site.
64
What are the functions of an alpha/beta barrel?
* Isomerisation of small sugars
* Oxidation by flavin coenzymes
* Phosphate transfer
* Degradation of sugar polymers
## Footnote
These functions are crucial for various biochemical processes.
65
What is unique about Glycolate oxidase in relation to barrels?
It is a barrel but is not open due to bulky hydrophobic amino acids
## Footnote
The specific arrangement of residues affects its structure.
66
Describe the residue types found in an α/β barrel.
Residues 1, 3, 5, etc. are bulky hydrophobic residues; residues 2, 4, 6, etc. are hydrophobic residues in the shell
## Footnote
This arrangement contributes to the structural integrity of the barrel.
67
What is Pyruvate kinase?
A large protein with multiple folds including an α/β barrel domain, a tetramerisation domain, and an open twisted α/β domain
## Footnote
It also contains an immunoglobulin fold.
68
What is the function of the Sandwich/Rossman fold?
Coenzyme binding domain of some hydrogenases and nucleotide binding domains
## Footnote
It features a doubly wound topology.
69
What is a Sandwich/Rossman or or α/β open twisted sheet?
Truncated TIM barrel with fewer than 8 helix/sheets that still has its functions.
Doubly would topology, which helices on both sides of the sheets, has a crevice between motif 1 and 2 that points you towards the active site.
70
What characterizes the Horseshoe fold?
Leucine-rich motifs, recognizable from the sequence and very flexible
## Footnote
It has too many repeats for a barrel and affects catalytic site positioning.
71
What are horseshoe folds primarily based on?
Leucine amino acids that hold together the strands and helices
## Footnote
These proteins serve various functions.
72
List some functions horseshoe folds.
* Receptors
* Cell adhesion
* Virulence factors
* RNA splicing
* DNA repair
## Footnote
Their diverse roles are important in cellular processes.
73
What is a Toll-like receptor?
Contains multiple horseshoe domains and leucine-rich repeats, involved in innate immunity
## Footnote
It plays a role in pattern recognition.
74
Alpha domain structures
* Coiled coil
* Four-helix bundle
* Globin fold
* alpha-alpha barrel
75
Coiled Coil
Two helices coiling around each other
Hydrophobic interactions between helices
Hydrophillic/charged amino acids on the outside to form salt links.
Can be identified from the sequence
76
Sequence of coiled coil
Repeating pattern of 7 amino acis (a-g)
Leucine in d
Isoleucine also common
Large amino acid in b
Charged e
77
How to tell which amino acids line up on the same face in a coiled coil?
Helical wheel plot
78
Leucine zipper
Example of a coiled coil
Unzipped part used to bind to DNA while zipped part is held together by hydrophobics and strengthened by ionic interactions.
79
SARS-CoV-2 spike protein
Has a α-β twisted sheet domain that interacts with the receptor.
Also has a stalk domain which consists of two coiled coil motifs.
So coiled coils are often structural proteins.
80
Four-helix bundle
Have similar characteristics to coiled coils.
Have hydrophobic face and hydrophilic face
Hydrophobic face holds helices together
Antiparallel helical conformation has 4 helices with hydrophobics on the inside.
Can occur the other way, with hydrophilic inside – membrane proteins
Not as restricted sequence as coiled coils
81
Cytochrome b562
has antiparallel, left twisted 4-helix bundles that can hold a haem
82
Helix bundles
Not restricted to just 4 helices, but they are the most common.
These α-helical bundles appear similar to β-barrels especially when they are transmembrane.
83
Globin Fold
Has specific orientations of helices in two different ways
4 α and β chains
Packing of the helices follows the ridges and grooves model
84
Ridges and grooves model
Orientation of amino acids along helix shows “ridges” every 4 amino acids
Or every 3rd amino acid forms another ridge
These ridges can be interlocked in different ways
+4n +4n ridges need to be tilted at 25 to have a nice alignment of ridges at 50
The +4n +3n can be tilted the other way at a 20 angle to get a nice arrangement of helices.
85
Alpha alpha barrel
All have barrel structure with helices going from outside to inside to outside etc
Have 6 helices on the inside and 6 helices in the outside
Alternating helices inside and outside
Odd on outside (at least sometimes)
86
Alpha alpha barrels and complements
Often occur in complements
Classical complement pathway important for interactions with cell membrane
3 complements have the alpha-alpha barrel thioester domain
87
Can we trust published macromolecular structures?
Most of the time, but not always
88
Spikes of influenza
Neuraminidase and Haemagglutinin
N1H1 is spanish flu
89
Action of spike proteins in influenza
virus is attached and taken up using H. Once the virus has proliferated it starts to bud and N cleaves the H attachments, to allow the virus to leave.
90
Hemagglutinin
Has a jelly roll structure
Fusion peptides change conformation to create a “piercing helix” to pierce into the membrane.
Conformational changes occur due to pH.
Interacts with salylic acid at the receptor
91
Neuraminidase
β-propeller which is 6 bladed. Individual blades contain 4 antiparallel βstrands.
Active site is in the centre of the propeller.
Close to viral surface there are long loops which are involved in the cleaving of sailic acid.
Sits on the surface of the virus as a tetramer.
92
Drug Design for Influenza
Often relies on making drugs that inhibit the sialic acid binding site on N
But the virus mutates.
