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Hydrophobically stabilized open state for the lateral gate of the Sec translocon

Zhang, Bin and Miller, Thomas F., III (2010) Hydrophobically stabilized open state for the lateral gate of the Sec translocon. Proceedings of the National Academy of Sciences of the United States of America, 107 (12). pp. 5399-5404. ISSN 0027-8424. PMCID PMC2851780. https://resolver.caltech.edu/CaltechAUTHORS:20100412-111115657

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Abstract

The Sec translocon is a central component of cellular pathways for protein translocation and membrane integration. Using both atomistic and coarse-grained molecular simulations, we investigate the conformational landscape of the translocon and explore the role of peptide substrates in the regulation of the translocation and integration pathways. Inclusion of a hydrophobic peptide substrate in the translocon stabilizes the opening of the lateral gate for membrane integration, whereas a hydrophilic peptide substrate favors the closed lateral gate conformation. The relative orientation of the plug moiety and a peptide substrate within the translocon channel is similarly dependent on whether the substrate is hydrophobic or hydrophilic in character, and the energetics of the translocon lateral gate opening in the presence of a peptide substrate is governed by the energetics of the peptide interface with the membrane. Implications of these results for the regulation of Sec-mediated pathways for protein translocation vs. membrane integration are discussed.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0914752107 DOIArticle
http://www.pnas.org/content/107/12/5399PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851780/PubMed CentralArticle
ORCID:
AuthorORCID
Zhang, Bin0000-0002-3685-7503
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2010 National Academy of Sciences. Edited by Gunnar von Heijne, Stockholm University, Stockholm, Sweden, and accepted by the Editorial Board February 5, 2010 (received for review December 31, 2009); published online before print March 4, 2010. The authors thank Todd Gingrich,William Clemons, and Tom Rapoport for helpful discussions. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the US Department of Energy under Contract DE-AC02-05CH11231. Author contributions: B.Z. and T.F.M. designed research, performed research, contributed new reagents/analytic tools, analyzed data, and wrote the paper.
Funders:
Funding AgencyGrant Number
Department of Energy (DOE)DE-AC02-05CH11231
Subject Keywords:coarse graining; free-energy landscape; hydrophobicity; membrane integration; protein translocation
Issue or Number:12
PubMed Central ID:PMC2851780
Record Number:CaltechAUTHORS:20100412-111115657
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20100412-111115657
Official Citation:Bin Zhang and Thomas F. Miller III Hydrophobically stabilized open state for the lateral gate of the Sec translocon PNAS 2010 107 (12) 5399-5404; published ahead of print March 4, 2010, doi:10.1073/pnas.0914752107
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17937
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:13 Apr 2010 17:51
Last Modified:09 Mar 2020 13:19

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