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Journal Article

The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins

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Itzhak,  Daniel N.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Sinitcyn,  Pavel
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Cox,  Jürgen
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Borner,  Georg H. H.
Borner, Georg / Systems Biology of Membrane Trafficking, Max Planck Institute of Biochemistry, Max Planck Society;

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elife-37018-v3.pdf
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Citation

Shurtleff, M. J., Itzhak, D. N., Hussmann, J. A., Oakdale, N. T. S., Costa, E. A., Jonikas, M., et al. (2018). The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins. eLife, 7: e37018. doi:10.7554/eLife.37018.


Cite as: http://hdl.handle.net/21.11116/0000-0002-7470-D
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.