Robinson, P. J. , Pringle, M. A. , Woolhead, C. A. and Bulleid, N. J. (2017) Folding of a single domain protein entering the endoplasmic reticulum precedes disulfide formation. Journal of Biological Chemistry, 292(17), pp. 6978-6986. (doi: 10.1074/jbc.M117.780742) (PMID:28298446) (PMCID:PMC5409466)
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Abstract
The relationship between protein synthesis, folding and disulfide formation within the endoplasmic reticulum (ER) is poorly understood. Previous studies have suggested 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Bulleid, Professor Neil and Pringle, Mrs Marie and Robinson, Dr Philip and Woolhead, Professor Cheryl |
| Authors: | Robinson, P. J., Pringle, M. A., Woolhead, C. A., and Bulleid, N. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Journal of Biological Chemistry |
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 |
| ISSN (Online): | 1083-351X |
| Published Online: | 15 March 2017 |
| Copyright Holders: | Copyright © 2017 y The American Society for Biochemistry and Molecular Biology, Inc |
| First Published: | First published in Journal of Biological Chemistry 292(17):6978-6986 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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