The endoplasmic reticulum (ER) exerts a quality control over newly synthesized proteins and a variety of components have been implicated in the specific recognition of aberrant or misfolded polypeptides. We have exploited a site-specific cross-linking approach to search for novel ER components that may specifically recognize the misassembled transmembrane domains present in truncated polytopic proteins. We find that a single probe located in the transmembrane domain of a truncated opsin fragment is cross-linked to several ER proteins. These components are distinct from subunits of the Sec61 complex and represent a ‘post-translocon’ environment. In this study, we identify one of these post-translocon cross-linking partners as the signal peptide peptidase (SPP). We find that the interaction of truncated opsin chains with SPP is mediated by its second transmembrane domain, and propose that this interaction may contribute to the recognition of misassembled transmembrane domains during membrane protein quality control at the ER.
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Research Article|
November 09 2004
A misassembled transmembrane domain of a polytopic protein associates with signal peptide peptidase
Samuel G. CRAWSHAW;
Samuel G. CRAWSHAW
*Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Bruno MARTOGLIO;
Bruno MARTOGLIO
†Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), ETH-Hoenggerberg, 8093 Zürich, Switzerland
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Suzanna L. MEACOCK;
Suzanna L. MEACOCK
1
*Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Stephen HIGH
Stephen HIGH
2
*Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
2To whom correspondence should be addressed (email stephen.high@manchester.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 20 2004
Revision Received:
September 08 2004
Accepted:
September 16 2004
Accepted Manuscript online:
September 16 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 384 (1): 9–17.
Article history
Received:
July 20 2004
Revision Received:
September 08 2004
Accepted:
September 16 2004
Accepted Manuscript online:
September 16 2004
Citation
Samuel G. CRAWSHAW, Bruno MARTOGLIO, Suzanna L. MEACOCK, Stephen HIGH; A misassembled transmembrane domain of a polytopic protein associates with signal peptide peptidase. Biochem J 15 November 2004; 384 (1): 9–17. doi: https://doi.org/10.1042/BJ20041216
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