Please use this identifier to cite or link to this item: doi:10.22028/D291-30508
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Title: Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import
Author(s): Nguyen, Duy
Stutz, Regine
Schorr, Stefan
Lang, Sven
Pfeffer, Stefan
Freeze, Hudson H.
Förster, Friedrich
Helms, Volkhard
Dudek, Johanna
Zimmermann, Richard
Language: English
Title: Nature Communications
Volume: 9
Issue: 1
Publisher/Platform: Nature Publishing Group
Year of Publication: 2018
Publikation type: Journal Article
Abstract: In mammalian cells, one-third of all polypeptides are transported into or across the ER membrane via the Sec61 channel. While the Sec61 complex facilitates translocation of all polypeptides with amino-terminal signal peptides (SP) or transmembrane helices, the Sec61-auxiliary translocon-associated protein (TRAP) complex supports translocation of only a subset of precursors. To characterize determinants of TRAP substrate specificity, we here systematically identify TRAP-dependent precursors by analyzing cellular protein abundance changes upon TRAP depletion using quantitative label-free proteomics. The results are validated in independent experiments by western blotting, quantitative RT-PCR, and complementation analysis. The SPs of TRAP clients exhibit above-average glycine-plus-proline content and below-average hydrophobicity as distinguishing features. Thus, TRAP may act as SP receptor on the ER membrane's cytosolic face, recognizing precursor polypeptides with SPs of high glycine-plus-proline content and/or low hydrophobicity, and triggering substrate-specific opening of the Sec61 channel through interactions with the ER-lumenal hinge of Sec61α.
DOI of the first publication: 10.1038/s41467-018-06188-z
URL of the first publication: https://www.nature.com/articles/s41467-018-06188-z
Link to this record: hdl:20.500.11880/28888
http://dx.doi.org/10.22028/D291-30508
ISSN: 2041-1723
Date of registration: 20-Mar-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
Collections:UniBib – Die Universitätsbibliographie

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