L2 - Higher levels of protein structure Flashcards
What is the next level of complexity after the secondary structure?
Super secondary structure or ‘motifs’
What is the super secondary structure or ‘motifs’?
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
What do motifs usually contain?
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
3 groups of loops/turns?
Beta-turn/bend
Omega loops
Disordered loops
Beta-turn/bend
Most often link beta-strands
Consist of 4 residues, 2 residues do not form H-bonds, 1 H-bond is formed per turn
Omega loops
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
Disordered loops
If it gets so big it becomes a disordered loop – we don’t understand the order
N & C termini plus internal linking secondary structure
Protein loops
Not defined by H bonding
Very variable & dependent upon local context & sequence
What are motifs?
Small definable elements of super secondary structure
4 examples of motifs
Anti-parallel beta-strand pair
Greek key
Helix bundle
Beta-alpha-beta motif
Anti-parallel beta-strand pair motif
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
Greek key motif
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
Helix bundle motif
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
Beta-alpha-beta motif
The beta-alpha-beta motif is represented as 2 parallel strands with a helix in-between
What does super secondary structure tell us?
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
How do secondary structures fit together?
They are quite limited & well defined with a limited number of interactions
Why do beta sheets twist?
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
How do beta-sheet twists affect folds?
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
Structure of thioredoxin in terms of beta sheets?
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
Do helix-helix interactions have limited angles?
Yes - alpha helices fit together in preferred conformations – not random
What are the 3 conformations of helix-helix interactions?
Practically right angle (105 degrees)
Something in between (52 degrees)
23 degrees
Conformation of helices in a 4 helix bundle
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
Helix-strand interactions
The twist in the beta sheet can sometimes create a groove suitable for the side chains of the alpha helix to fit into
What are motifs?
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