Protein Structure and Protein Folding

Question 1

What is super secondarystructure and some examples?

Answer 1

elements of secondary structure ie. helices and strands, are connected by turns or by region of less ordered structure called loops or coils to make up supersecondary structure

Examples:
- Helix-turn-helix
- beta hairpin
- greek key (4 antiparallel strands)
- strand - helix - strand

Question 2

what are protein domains?

Answer 2

super secondary structure elements combine to form domains which are independently folded regions that often possess as specific function within the protein.
domains then come together to make a whole protein
- typically has a hydrophobic core, which is very important for protein stability

Question 3

outline the steps involved in protein folding of a newly synthesised protein

Answer 3

Protein folding is directed largely by its internal hydrophobic residues, which form an internal hydrophobic core, while hydrophilic residues are solvent exposed.
NOT a random process:
1. formation of short secondary structure elements
2. subdomains form
3. subdomains come together to form a partially folded domain; a ‘molten globule’ the can rearrange (tertiary structure still partially disordered)
4. final domain structure emerges, small conformational adjustments to give final compact native structure.
Non-covalent interations collectively make a significant contribution to protein conformation stability.

Question 4

what are chaperones?

Answer 4

they help with folding

i) chaperone-independent
ii) chaperone-dependent eg. Hsp 70
iii) chaperonin-dependent eg. GroEL-GroES

Question 5

describe prion diseases

Answer 5

Prion diseases: brain conditions where protein PrP changes shape and then forms aggregates that can cause damage (fatal)
- borine spongiform encephalopathy (BSE)
- Creutzfeldt-Jacob disease (CJD)
- kuru

• The proteins that cause the problems are called prions for ‘proteins infectious agent’
• It is though that the abnormal form of a prion protein, PrP, induces the normal form of this protein to become misfolded
• alpha to beta transformation occurs in the abnormal protein
• no treatment available, always fatal

Question 6

Describe the features of a beta hairpin

Answer 6

• common
• antiparallel
• length varies

Question 7

what are three examples of families that proteins can be grouped into based on structure?

Answer 7

alpha domain family:
- amphipathic helices with side chins packed closely together within a hydrophobic core
- mostly helical
Eg. globin fold

alpha/beta family:
- a mix of alpha and beta structure

antiparallel beta family:
- mostly antiparallel beta structure
eg. retinal binding protein

Question 8

What did the Anfinsen experiment prove? and what was the process?

Answer 8

Proved that the only ‘instructions’ needed or folding were imbedded in the amino acid sequence of the polymer

• Got a protein
• Denatured it
• got ride of urea and a type of ethanol
• It folded itself back up naturally

Question 9

Describe the stabilisation of protein folding

Answer 9

• Non-covalent interactions, while individually weak in proteins, collectively make a significant contribution to protein conformational stability
• In some proteins additional covalent bonds (for example, disulphide bonds) may be present that contribute to conformation stability
• The hydrophobic core is likely the most important noncovalent contributor to protein stability in aqueous solution

Question 10

Describe misfolding of proteins in disease

Answer 10

amyloid protein misfolding thought to contribute to:
- Alzheimers
- Type 2 Diabetes

Prions are not involved in these ailments