Lecture 13

Question 1

broad substrate specificity

Answer 1

there is no recognition of a particular primary SP sequence instead its general features e.g. hydrophobic stretch and positive AA near N’ terminus

Question 2

what does the specificity of ER targeting depend on?

Answer 2

broad substrate specificity in the recognition step
the folding of SP into a loop by SRP which allows signal peptidase to cleave the signal within the translocon releasing the SP into the ER membrane which is removed by SPP

Question 3

what is the signal peptide cleaved by?

Answer 3

signal peptide is cleaved off by signal peptidase

Question 4

N glycosylation

Answer 4

covalent addition of an oligosaccharide tree of sugars from a lipid carrier to the N atom of a target asparagine side chain of ER proteins that encode an ER proteins that encode an N-glycosylation signal (N-X-Ser/Thr) by the membrane-integral) OST.

Question 5

Why are N-glycans attached to proteins?

Answer 5

1. core N glycan is very large and made of hydrophilic sugars - increase protein solubility and can reduce aggregation problems during folding
2. N glycans are bulky - contrain alpha carbon backbone of the polypeptide and influence folding rates and final protein conformation, and influence activity of protein
3. act as flags for folding and ER quality control. removal of glc residues from N-oligosaccharide in the ER allows interaction with ER chaperones e.g. calreticulin required for efficient folding of N-glycosylated proteins

Question 6

what are 3 other secretory system modification

Answer 6

1. O-glycosylation
2. proteolytic cleavage (albumin cleaved by cleavage)
3. addition of lipids for membrane targeting (GPCRs)