Endoplasmic Reticulum

What is the Sec 61 translocon?

bundle of 10 α helices, 4 transmembrane domains form a lateral gate into the membrane, the cytosolic side binds the ribosome, laminal side includes short α helix (plug), translocating peptide dislodges plug

What is the signal sequence?

chain of 6-12 hydrophobic amino acid residues neighboring a basic amino acid

What is a membrane spanning segment?

α helices containing 20-25 hydrophobic amino acids

Type 1 membrane protein

cleavable signal sequence, ~22 hydrophobic amino acids that fold on to an α helix, NTD in the lumen

Type 2 membrane protein

no signal sequence, positively charged NTD in cytosol

Type 3 membrane protein

no signal sequence, positively charged CTD in cytosol, short NTD

Type 4 membrane protein

moves through translocon until next α helix is formed, even # of α helices: NTD and CTD on same side, odd# of α helices: NTD and CTD on opposite sides

GPI anchor membrane protein

requires ATP hydrolysis, GET 3 binds to hydrophobic CTD, GET 1 and GET 2 insert protein into membrane

BiP

ER chaperone, Hsp70 type

IRE1

cleaves mRNAs to reduce ER protein folding load

PERK

initiates translation of eIF2 and arrests global protein synthesis

ATF6

transcription factor that drives expression of unfolded protein response genes

Calnexin/calreticulin

bind N-linked oligosaccharides, so UGGT can readd a glucose

OS9/XTP2B

binds mannose trimmed N-linked oligosaccharides and targets for degradation by bringing through translocon

ERAD

temporally and spatially coordinated surveillance process that clears aberrant proteins in ER

mannosidases

remove mannose from unfolded proteins