L2 - Higher levels of protein structure

Question 1

What is the next level of complexity after the secondary structure?

Answer 1

Super secondary structure or ‘motifs’

Question 2

What is the super secondary structure or ‘motifs’?

Answer 2

These things are recognisable building blocks of proteins

They are stable subunits that fit together to form proteins

By understanding these, the variety of protein structures is not as great as once though – more tractable & understandable

Question 3

What do motifs usually contain?

Answer 3

Motifs usually contain loops or turns
• Turns are short & defined by H bonds
• Loops are long & ill-defined

These nonregular secondary structures are not random or disordered
They are simply harder to describe

Question 4

3 groups of loops/turns?

Answer 4

Beta-turn/bend

Omega loops

Disordered loops

Question 5

Beta-turn/bend

Answer 5

Most often link beta-strands

Consist of 4 residues, 2 residues do not form H-bonds, 1 H-bond is formed per turn

Question 6

Omega loops

Answer 6

Found in most large proteins

Is longer than a beta-turn but stable & functional

Compact globular entities which fill their internal empty spaces with side chains

Question 7

Disordered loops

Answer 7

If it gets so big it becomes a disordered loop – we don’t understand the order

N & C termini plus internal linking secondary structure

Question 8

Protein loops

Answer 8

Not defined by H bonding

Very variable & dependent upon local context & sequence

Question 9

What are motifs?

Answer 9

Small definable elements of super secondary structure

Question 10

4 examples of motifs

Answer 10

Anti-parallel beta-strand pair

Greek key

Helix bundle

Beta-alpha-beta motif

Question 11

Anti-parallel beta-strand pair motif

Answer 11

A simple motif

Beta strands cannot exist by themselves

Has to have H bonds to stabilise it (in both directions)

H bonds are maintained by an antiparallel strand

Question 12

Greek key motif

Answer 12

Sometimes the order of the beta strands isn’t always a simple meander – can be a Greek key motif

Is still antiparallel but it has a beta strand pair which has been inserted in-between the other 2

Due to the way it forms in 3-dimensional space

Question 13

Helix bundle motif

Answer 13

The alpha helix is different to the beta structure as it folds by itself – doesn’t need to H bond to other alpha helices for stability

Question 14

Beta-alpha-beta motif

Answer 14

The beta-alpha-beta motif is represented as 2 parallel strands with a helix in-between

Question 15

What does super secondary structure tell us?

Answer 15

They tell us how bits of secondary structure are arranged in proteins relative to each other

There are defined ways in which secondary structure fit together – it is not random

Question 16

How do secondary structures fit together?

Answer 16

They are quite limited & well defined with a limited number of interactions

Question 17

Why do beta sheets twist?

Answer 17

Because beta-sheets are formed from L-amino acids it has the effect of inducing a reproducible twist in the strands which then causes the whole sheet to bend

Can be as extreme as 30 degrees per residue in extended antiparallel beta-strand pairs

Question 18

How do beta-sheet twists affect folds?

Answer 18

Antiparallel = flat H bonds
Parrallel = less straight & weaker H bonds
Can be mixed together

Has a pronounced twist – propeller twist

Very few beta sheets are flat – most of them have some kind of twist

Question 19

Structure of thioredoxin in terms of beta sheets?

Answer 19

Thioredoxin is an essential protein which controls oxidation in the cell

It has a mixed anti-parallel & parallel beta sheet at its core which adopts a constant twist that looks like a propeller

Question 20

Do helix-helix interactions have limited angles?

Answer 20

Yes - alpha helices fit together in preferred conformations – not random

Question 21

What are the 3 conformations of helix-helix interactions?

Answer 21

Practically right angle (105 degrees)

Something in between (52 degrees)

23 degrees

Question 22

Conformation of helices in a 4 helix bundle

Answer 22

In a 4 helix bundle each alpha helix is about 23 degrees from each other – fit better together in this orientation

Makes life simpler for us – most helices fit in particular ways

Protein folds because they are stable molecules & these 3 ways are the most stable ways for the protein to fold

Restricts the variety

Question 23

Helix-strand interactions

Answer 23

The twist in the beta sheet can sometimes create a groove suitable for the side chains of the alpha helix to fit into

Question 24

What are motifs?

Answer 24

Motifs are small structures whose folding pattern is made up of simple & often recurring arrangements of secondary structure

Motifs are unlikely to exist alone & when added together form recognisable folds

Question 25

What is a fold?

Answer 25

A fold is a complete structure able to exist either by itself or as part of a multi-domain protein

Some proteins are made up of multiple different folds – these are called domains within a protein

Question 26

Jelly (or Swiss) Roll Barrel

Answer 26

This is a fold as can sit by itself

This is a beta barrel that isn’t just a meander – a complicated Greek key structure

It is composed of lots of beta hairpins that fit together

Question 27

What happens if a beta sheet folds around itself?

Answer 27

Beta-sheets can curl & form Beta-barrels

Beta barrel is a fold

Question 28

Beta rich structures can form large repetitive architectures such as:

Answer 28

• Sandwich
• 3 Solenoid
• 5 bladed propeller
• Clam

Question 29

Relationship between motifs and folds?

Answer 29

The same motifs can form different folds

Question 30

Tertiary structure of proteins

Answer 30

Tertiary structure is composed of folds in which secondary structures are linked by turns, loops & disordered regions

Larger proteins may appear to consist of 2 or more distinct folds thus referred to as domains of that protein

Question 31

Hierarchy of protein structure

Answer 31

The hierarchy is defined by the rigidity of the peptide bonds & H bonds demands

End up with either an alpha helix or a beta sheet as the secondary structure

We then have a certain number of repetitive ways to fit them together to form motifs

Can then see defined folds which either make up whole proteins or domains within proteins

Question 32

What are domains?

Answer 32

A protein domain is a conserved part of a given protein sequence and tertiary structure that can evolve, function, and exist independently of the rest of the protein chain

Function follows domains
Helps us with evolution