3D Structure of Proteins

Question 1

what is the folding of the polypeptide determined by?

Answer 1

• aa sequence
• molecular structure and properties of aa
• molecular environment

Question 2

how are aa categorised by?

Answer 2

their structural and chemical properties

Question 3

what are some of the categories of aa?

Answer 3

• un/charged (+ve or -ve)
• hydrophobic or hydrophilic
• acidic or basic

Question 4

name some charged aa

Answer 4

aspartic acid, glutamic acid, arginine

Question 5

stability of the folding depends on the bonds.

what are the two types?

Answer 5

• covalent bonds

- non-covalent bonds

Question 6

what are the 4 main non-covalent bonds?

Answer 6

• H bonds
• van de waals
• electrostatic attractions
• hydrophobic interactions

Question 7

what are the properties of disulfide bonds?

Answer 7

• disulfide bonds form between the side chains of two cysteine residues.
• the bonds form in an oxidative reaction forming very strong covalent bonds.
• the SH groups from each cysteine cross link.
• this usually occurs in distant parts of the amino acid sequence, but occurs adjacently in the three-dimensional structure.
• disulfide bonds can form on the same (intra-chain) or different (inter-chain) polypeptide chains (eg. insulin left).

Question 8

what happens when there is a protein mis-folding?

Answer 8

-reduction in protein function
-cellular processing that leads to degradation
-can lead to diseases:
huntingtons, alzheimers, parkinsons

Question 9

what are the possible causes of protein mis-folding?

Answer 9

• somatic mutations: leads to production of a proteins being unable to adopt native folding
• errors in transcription or translation: production of modified proteins
• failure of folding: environmental stimulus causes some proteins to denature
• errors in post translational modifications: glycosylation, phosphorylation
• structural modification: ionic environment or heat stress
• induction proteins mis-folding: seeding and cross-seeding

Question 10

how does mis-folding lead to Alzheimers?

Answer 10

• proteolytic cleavage of the amyloid precursor protein (APP)
• APP is involved in G protein signalling
• cleavage of APP causes β-amyloid (A β) to be released
• accumulation of A β causes protein to mis-fold and form β pleated sheets

Question 11

what causes cystic fibrosis?

Answer 11

• deletion of phenylamine residue of cystic fibrosis transmembrane conductance regulator (CFTR)
• leads to mis-folding in ER
• causes ubiquitylation and degradation of proteins

Question 12

what are prions?

Answer 12

mis-folded proteins (PrPsc) that interact w normal proteins (PsPc)

Question 13

what do prions do?

Answer 13

induce the mis-folding of normal proteins