L3 - Higher levels of protein structure II

Question 1

Interaction between domains

Answer 1

Domains interact to a lesser extent with each other – linker sequences connect them

Question 2

Structure of domains

Answer 2

Mostly spherical entities - why they’re called globular proteins

< 200 amino acids

Can be functional units

Question 3

How apparent are protein domains?

Answer 3

Isn’t always easy to tell how a protein has been built up

Question 4

What are bacterial toxins?

Answer 4

They are multi domain proteins that have evolved by the acquisition of different domains

Question 5

Bacterial toxin example

Answer 5

The anthrax toxin is a protective antigen (used as a vaccine) that enters into cells & enters into cells & causes toxicity & kills eukaryotic cells

Each domain has a different role

Each one is a defined structure

Evolution goes a lot more quickly if you can adopt pre-formed structures

Question 6

What is IgG?

Answer 6

Antibody composed of immunoglobulin like domains

Question 7

Immunoglobulin like domains

Answer 7

Do get repetitive structures in biology which appear to have nothing to do with each other in evolution

Come to the conclusion that some of them are useful structures

Eg. the Ig is a good way of folding up proteins to make a robust & readily folded structure

Ig is a very widespread building block in biology

Question 8

What is Titin?

Answer 8

The biggest protein - made of 30000 AA but is very repetitive

Titin goes between the Z discs in muscles & is the protein that stops muscles extending too far – molecular ruler in the muscles

Mainly immunoglobulin domains

Question 9

Why are there so many immunoglobulin domains in Titin when they are not associated with antibodies?

Answer 9

Through evolution, it must’ve been an advantage to extend the distance between the Z discs in the muscle, & as this happened Titin was extended by the addition of some immunoglobulin domains

By gene splicing this can happen very readily

• This has nothing to do with antibodies
• They are good structures

Question 10

Where else can immunoglobulin domains be found?

Answer 10

T-cell surface glycoprotein CD4 - is an antibody

Titin

Yersina pestis capsular antigen

Question 11

Yersina pestis capsular antigen and immunoglobulin domains

Answer 11

Bacteria that caused the black death

Uses Ig domains to protect itself from the immune system – there’s no sequence homology just appears to carry out the function, the bacteria has adopted this structure

Needs to be tough and this type of molecule doesn’t stretch

Question 12

What does the common use of immunoglobulin domains in lots of different proteins tell us?

Answer 12

If several organisms have come up with the same solution independently it tells us that its doing it because of the properties of the protein fold

They are now so dispersed we don’t know whether they’re related to each other or not

Question 13

Why do we classify proteins according to structure?

Answer 13

Since proteins evolve by adding domains, we can classify proteins by which folds they contain, making them easier to understand

This enables us to understand protein folding, evolution & function

Question 14

What are the 3 classes are proteins classified into?

Answer 14

Alpha helical only

Beta sheet only

Folds that are separate alpha and beta sections or interspersed alpha and beta sections (alpha I beta)

Question 15

What can the beta sheet class be broken down into?

Answer 15

Parallel
Orthogonal
Others

This is the tertiary structure

Question 16

The structural classification of proteins

Answer 16

CATH

Class
Architecture
Topology
Homologous superfamilies

Question 17

Structural classification of proteins - Class

Answer 17

Derived from secondary structure content

Question 18

Structural classification of proteins - Architecture

Answer 18

Gross orientation of secondary structures, independent of connectivities (eg. not linked)

Architecture is simply the arrangement of the bits of secondary structure – doesn’t describe any of the linkages

Question 19

Structural classification of proteins - Topology

Answer 19

Clusters structures according to their topological connections & numbers of secondary structures

Proteins with different topology’s cannot have evolved from each other – strong indication of relationships in evolution – strong indication that rules drive protein evolution into segments

Likely to evolved separately telling us it’s a good stable design to make a protein

Ones that look very similar can have very different amino acids so can put them into different super families

Question 20

Structural classification of proteins - Homologous superfamilies

Answer 20

Cluster proteins with highly similar structures & functions

Question 21

What is 2 proteins have the same architecture but have different topologies?

Answer 21

They have different folds

Question 22

How is the number of protein folds limited?

Answer 22

The number of possible proteins is almost unlimited: eg. 20^200 different sequences for a 200aa protein

The number of protein folds is however relatively small: ~10000

Distribution of proteins among folds is non-homogenous: some folds are extremely abundant (superfolds) but many are rare (unifolds)

Question 23

Possible explanation for the limit to protein folds?

Answer 23

Limited number of stable secondary structural elements

Many non-homologous sequences can have the same fold

Limited ways of interaction between them

The tendency to compactness limits the length of secondary structural elements

Divergent rather than convergent evolution