Proteomics reveals signal peptide features determining the client specificity 
in human TRAP-dependent ER protein import

Nguyen, Duy; Stutz, Regine; Schorr, Stefan; Lang, Sven; Pfeffer, Stefan; Freeze, Hudson H.; Foerster, Friedrich; Helms, Volkhard; Dudek, Johanna; Zimmermann, Richard

doi:10.1038/s41467-018-06188-z

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import

MPS-Authors

/persons/resource/persons78500

Pfeffer, Stefan
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource

https://www.nature.com/articles/s41467-018-06188-z#Sec20
(Supplementary material)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

s41467-018-06188-z.pdf
(Publisher version), 3MB

Supplementary Material (public)

There is no public supplementary material available

Citation

Nguyen, D., Stutz, R., Schorr, S., Lang, S., Pfeffer, S., Freeze, H. H., et al. (2018). Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import. Nature Communications, 9: 3765. doi:10.1038/s41467-018-06188-z.

Cite as: https://hdl.handle.net/21.11116/0000-0002-F3EF-F

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 Sec61auxiliary 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 substratespecific opening of the Sec61 channel through interactions with the ER-lumenal hinge of Sec61 alpha.