User:ERQC

ER Quality Control

Literature Review Ero1p: A Novel and Ubiquitous Protein with an Essential Role in Oxidative Protein Folding in the Endoplasmic Reticulum

Ero1p: A Novel and Ubiquitous Protein with an Essential Role in Oxidative Protein Folding in the Endoplasmic Reticulum Pollard MG, Travers KJ, Weissman JS Mol. Cell. 1998

Major conclusions: 1) Ero1p: essential ER-resident protein          2) mutations to Ero1p cause sensitivity to DTT, overexpression causes DTT resistance 3) Ero1p defects result in ER retention of reduced nonnative disfuldie-stabilized proteins, disfulide free protein are not affected

Introduction: Interesting criteria for protein folding within the ER            1) No "chaperonins" involved  (ie GroEL)           2) Glycosylation accompanies folding 3) Insertion of transmembrane domains into the ER membrane          4) oxidation of cysteines to make disulfide bonds

The redox potential of the ER is tuned to be optimal for PDI mediated folding of ribonuclease A in vitro. Conceptually, the redox potential must be kept within in a certain window because if too reducing, disulfide bonds will not form, but if too oxidizing, incorrect linkages cannot be isomerized.

Big Question for this paper: What is the molecular basis for the ER oxidoreductase system?
Screen 1: Screen for proteins that confer resistance to DTT when overexpressed. Method: Transform yeast with high copy genomic plasmic library and select for transformants that allow growth on plates containing 8mM DTT From this screen found ERO1

Glossary of Terms:

Ire1

Hac1

PDI

Ero1