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

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

Content Provider	Scilit
Author	Robinson, Philip J. Pringle, Marie Anne Woolhead, Cheryl A. Bulleid, Neil J.
Copyright Year	2017
Description	Journal: Journal of Biological Chemistry 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.
Related Links	http://www.jbc.org/content/292/17/6978.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409466/pdf http://www.jbc.org/article/S0021925820428881/pdf
Ending Page	6986
Page Count	9
Starting Page	6978
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m117.780742
Journal	Journal of Biological Chemistry
Issue Number	17
Volume Number	292
Language	English
Publisher	Elsevier BV
Publisher Date	2017-04-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Disulfide Formation Endoplasmic Reticulum Protein Disulfide Isomerase Protein Translocation
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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