Module 2: V10 - V12

Question 1

What is a subunit?

Answer 1

a polypeptide chain

Question 2

What is the primary structure of a protein?

Answer 2

the amino acid sequence

Question 3

What is the secondary structure of a protein?

Answer 3

the elements, ɑ-helices, β-sheets and turns (also simple motifs ɑ-ɑ, β-β, β-ɑ-β which are supersecondary structures)

Question 4

What is the tertiary structure of a protein?

Answer 4

the overall spatial arrangement of atoms in a protein i.e. describes the fold of a protein chain/subunit (domains/folds/modules and arrangement of domains)

Question 5

How is the tertiary structure of a protein stabilised?

Answer 5

stabilised by numerous weak interactions between amino acid side chains (e.g. hydrophobic and polar interactions + disulfide bonds)

Question 6

How is a quaternary structure formed?

Answer 6

by the assembly of individual polypeptides into a larger functional cluster
i.e. the arrangement of two or more protein subunits

Question 7

What is a domain?

Answer 7

a region within the native tertiary structure for which evidence can be provided of an existence independent of the rest of the protein (fold independently)
a single protein chain can consist of one or more domains

Question 8

What is a fold?

Answer 8

defined by the arrangement of secondary structure elements relative to each other in space

Question 9

What is a module?

Answer 9

protein domains which have one or more repeating folds within their overall structure

Question 10

What do modules do?

Answer 10

they can attribute a function to individual folds: catalytic, lipid-binding, peptide-binding, DNA binding, fibronectin-binding, transmembrane, etc.

Question 11

How are new proteins with new functions made?

Answer 11

by mixing domains and mutating existing domains

Question 12

What is intragenic mutation?

Answer 12

point mutations, insertions and deletions

Question 13

What is gene duplication?

Answer 13

duplication a whole genome or part of a genome

Question 14

What is DNA segment shuffle?

Answer 14

when two or more existing genes are broken and recombined

Question 15

What is lateral gene transfer?

Answer 15

when one organism acquires parts of the genome of another

Question 16

Can a domain be defined as an evolutionary unit or a structural unit?

Answer 16

an evolutionary unit

Question 17

How do new proteins evolve?

Answer 17

by gene duplication and domain shuffling

Question 18

Are new domains ever being created?

Answer 18

no, new domains are only ever being modified and readjusted as they are subjected to point mutations, insertions and deletions (change, gain and loss of function)

Question 19

How are sequences of protein domains compared?

Answer 19

they are compared based on identity or similarity

Question 20

What is meant by identity?

Answer 20

means exactly the same residue (invariant)

Question 21

What is meant by similar?

Answer 21

means a change to a residue that is observed frequently or with similar physical-chemical properties e.g. Ser to Thr, Val to Leu (conservative)

Question 22

How can alignments be improved? What does realignment account for?

Answer 22

by introducing gaps that account for residue insertions and deletions

Question 23

How do the structures of proteins that are related by evolutionary events such as gene duplication, but have different sequences, compare?

Answer 23

each sequence “change” results in a small change to structure, however, structure changes much more slowly than sequence which means that for two proteins whose sequences show >25% identity they will have similar structure

Question 24

What will gaps between two sequences result in?

Answer 24

a loop insertion within the general structural fold

Question 25

What are homologues?

Answer 25

protein domains that have sequences which show >25% identity (similar ancestry/they have the same fold)

Question 26

What are the two groups of homologues?

Answer 26

orthologues and paralogues

Question 27

What are orthologues?

Answer 27

homologous proteins that perform the same function in different species e.g. horse and tuna trypsin

Question 28

What are paralogues?

Answer 28

homologous proteins that perform different but related functions within one organism e.g. human trypsin, compared with human thrombin

Question 29

What does it mean if sequence identity is low «25% and the proteins are functionally different?

Answer 29

it is hard to draw conclusions

if we find the fold to be similar then they are likely to be homologues

Question 30

Define the term “protein domain” in terms of folding and structure.

Answer 30

the term “protein domain” refers to a region within the native tertiary structure which folds independently of the rest of the protein

Question 31

Antibodies are Y-shaped heterotetramers composed of two light chains and two heavy chains. Discuss the secondary, tertiary and quaternary structure of antibodies.

Answer 31

secondary structures = ɑ-helices, β-sheets, turns and simple motifs (ɑ-ɑ, β-β, β-ɑ-β)
tertiary structures = individual light chain and heavy chain segments which would fold independently of one another + be consisted of different unique polypeptide chains
quaternary structure = assembly of the heavy and light chains into a functional protein

Question 32

What are four genetic mechanisms that can give rise to new proteins with new functions?

Answer 32

intragenic mutation, gene duplication, DNA segment shuffle and lateral gene transfer

Question 33

What is the difference between sequence identity and sequence similarity? Give an example of similarity.

Answer 33

sequence identity means that the residues are exactly the same while sequence similarity means a change to a residue that is observed frequently or with similar physical-chemical properties e.g. Ser to Thr, Val to Leu

Question 34

The amino acid sequences of two different enzymes from two different species have 30% sequence identity. What can you safely say about these two proteins?

Answer 34

that they are homologues and have similar ancestry/are folded in a similar manner