In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-05-29)
Abstract:
The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain (TMD) lengths and hydrophobicity. Features in transmembrane domains such as charged residues in ion channels are often functionally important, but could pose a challenge during cotranslational membrane insertion and folding. Our systematic proteomic approaches in both yeast and human cells revealed that the ER membrane protein complex (EMC) binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally and immediately following clusters of TMDs enriched for charged residues. The EMC can remain associated after completion of translation, which both protects clients from premature degradation and allows recruitment of substrate-specific and general chaperones. Thus, the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade-off between function and stability.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.37018.001
DOI:
10.7554/eLife.37018.002
DOI:
10.7554/eLife.37018.003
DOI:
10.7554/eLife.37018.004
DOI:
10.7554/eLife.37018.006
DOI:
10.7554/eLife.37018.005
DOI:
10.7554/eLife.37018.007
DOI:
10.7554/eLife.37018.008
DOI:
10.7554/eLife.37018.009
DOI:
10.7554/eLife.37018.010
DOI:
10.7554/eLife.37018.011
DOI:
10.7554/eLife.37018.012
DOI:
10.7554/eLife.37018.013
DOI:
10.7554/eLife.37018.014
DOI:
10.7554/eLife.37018.022
DOI:
10.7554/eLife.37018.023
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3