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Residue-by-residue analysis of cotranslational membrane protein integration in vivo

Nicolaus, Felix and Metola, Ane and Mermans, Daphne and Liljenström, Amanda and Krč, Ajda and Abdullahi, Salmo Mohammed and Zimmer, Matthew and Miller, Thomas F., III and Von Heijne, Gunnar (2020) Residue-by-residue analysis of cotranslational membrane protein integration in vivo. . (Unpublished)

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We follow the cotranslational biosynthesis of three multi-spanning E. coli inner membrane proteins in vivo using high-resolution Force Profile Analysis. The force profiles show that the nascent chain is subjected to rapidly varying pulling forces during translation, and reveal unexpected complexities in the membrane integration process. We find that an N-terminal cytoplasmic domains can fold in the ribosome exit tunnel before membrane integration starts, that charged residues and membrane-interacting segments such as re-entrant loops and surface helices flanking a transmembrane helix (TMH) can advance or delay membrane integration, and that point mutations in an upstream TMH can affect the pulling forces generated by downstream TMHs in a highly position-dependent manner, suggestive of residue-specific interactions between TMHs during the integration process.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Miller, Thomas F., III0000-0002-1882-5380
Von Heijne, Gunnar0000-0002-4490-8569
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. Posted September 28, 2020. This work was supported by grants from the Knut and Alice Wallenberg Foundation (2012.0282), the Novo Nordisk Fund (NNF18OC0032828), and the Swedish Research Council (621-2014-3713) to GvH, and from NIGMS, National Institutes of Health, (R01GM125063) to TFM and MZ. This work used the Extreme Science and Engineering Discovery Environment (XSEDE) Bridges computer at PSC through allocation TGMCB160013. XSEDE is supported by National Science Foundation grant number ACI1548562. We thank Dr. Rickard Hedman (Stockholm University) for programming and maintenance of the EasyQuant software. The authors have declared no competing interest.
Funding AgencyGrant Number
Knut and Alice Wallenberg Foundation2012.0282
Novo Nordisk FundNNF18OC0032828
Swedish Research Council621-2014-3713
Record Number:CaltechAUTHORS:20200929-122616290
Persistent URL:
Official Citation:Residue-by-residue analysis of cotranslational membrane protein integration in vivo. Felix Nicolaus, Ane Metola, Daphne Mermans, Amanda Liljenstrom, Ajda Krc, Salmo Mohammed Abdullahi, Matthew Zimmer, Thomas F Miller III, Gunnar Von Heijne. bioRxiv 2020.09.27.315283; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105636
Deposited By: Tony Diaz
Deposited On:29 Sep 2020 20:12
Last Modified:29 Sep 2020 20:12

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