Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation.

Content Provider	Europe PMC
Author	Robinson, Philip J. Pringle, Marie Anne Woolhead, Cheryl A. Bulleid, Neil J.
Copyright Year	2017
Abstract	The relationship between protein synthesis, folding, and disulfide formation within the endoplasmic reticulum (ER) is poorly understood. Previous studies have suggested that pre-existing disulfide links are absolutely required to allow protein folding and, conversely, that protein folding occurs prior to disulfide formation. To address the question of what happens first within the ER, that is, protein folding or disulfide formation, we studied folding events at the early stages of polypeptide chain translocation into the mammalian ER using stalled translation intermediates. Our results demonstrate that polypeptide folding can occur without complete domain translocation. Protein disulfide isomerase (PDI) interacts with these early intermediates, but disulfide formation does not occur unless the entire sequence of the protein domain is translocated. This is the first evidence that folding of the polypeptide chain precedes disulfide formation within a cellular context and highlights key differences between protein folding in the ER and refolding of purified proteins.
ISSN	00219258
Volume Number	292
PubMed Central reference number	PMC5409466
Issue Number	17
PubMed reference number	28298446
Journal	The Journal of Biological Chemistry [J. Biol. Chem]
e-ISSN	1083351X
DOI	10.1074/jbc.M117.780742
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2017-03-15
Publisher Place	U.S.A.
Access Restriction	Open
Rights License	Author's Choice—Final version free via Creative Commons CC-BY license. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Subject Keyword	disulfide disulfide formation endoplasmic reticulum ER protein disulfide isomerase protein folding protein translocation β2-microglobulin
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry