Miles - Protein Synthesis II: Folding, Processing, ER Flashcards
Chaperones
Help mediate proper folding
Hsp70
ATP-dependent
Binds and covers hydrophobic patches to protect from misfolding or clumping
Protein disulfide isomerase
Cystine bridges
Peptidyl Prolyl Isomerase
Convert trans-cis changes in peptide bonds
What occurs to the initiator MET?
What terminus does this occur at?
It is removed via proteolysis from the N-terminus
What allows proteins to be targeted for transport to specific locations?
N-terminal signal sequences
Glycosylation
Occurs in ER, N-linked occurs on asparagine residues during cotranslational translocation into ER
Calnexin and Calreticulin
Binds N-linked residue site when one glucose remains, prevents last removal
Folding sensor examines protein, adds glucose back if not properly folded
GPI Anchors
Attach proteins to the luminal side of the ER membrane
N-myristoylation
Myristic acid attached to N-terminal glycine residue–cytostolic can impair plasma membrane embedding
Prenylation
Addition of lipid
Prenyl group attached to C-terminal cysteine residue
Palmitoylation
Addition of lipid
Palmitic acid attached to internal cysteine residue
What AAs are the targets for phosphorylation?
Serine
Threonine
Tyrosine
Nitrosylation
Addition of NO groups to internal cysteine
Unfolded Protein Response (UFR)
Excess of unfolded proteins activate UFR pathway.
Leads to expansion of ER, + chaperones, and apoptosis if shit gets really bad
Degradation of Proteins
Ubiquitin attached to side chain of lysine residue, targets protein for degradation. The more ubiquitation = more likely to be degraded.
Prion Disorders
You know these..
Infection with misfolded protein stimulates other proteins to misfold
Alzheimer’s
Amyloid plaques, similar to prion derived
Alpha-1 Antitrypsin Disorder
Defect of a protease inhibitor, emphysemes, smoking makes worse for heterozygotes
