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Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon

Niesen, Michiel J. M. and Zimmerman, Michael H. and Miller, Thomas F., III (2020) Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon. Journal of the American Chemical Society, 142 (12). pp. 5449-5460. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20200304-160026575

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Abstract

An important aspect of cellular function is the correct targeting and delivery of newly synthesized proteins. Central to this task is the machinery of the Sec translocon, a transmembrane channel that is involved in both the translocation of nascent proteins across cell membranes and the integration of proteins into the membrane. Considerable experimental and computational effort has focused on the Sec translocon and its role in nascent protein biosynthesis, including the correct folding and expression of integral membrane proteins. However, the use of molecular simulation methods to explore Sec-facilitated protein biosynthesis is hindered by the large system sizes and long (i.e., minute) timescales involved. In this work, we describe the development and application of a coarse-grained simulation approach that addresses these challenges and allows for direct comparison with both in vivo and in vitro experiments. The method reproduces a wide range of experimental observations, providing new insights into the underlying molecular mechanisms, predictions for new experiments, and a strategy for the rational enhancement of membrane protein expression levels.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.9b07820DOIArticle
ORCID:
AuthorORCID
Niesen, Michiel J. M.0000-0002-9255-6203
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2020 American Chemical Society. Received: July 22, 2019; Published: March 4, 2020. We gratefully acknowledge support from the National Institutes of Health (R01GM125063) and the Office of Naval Research (N00014-16-1-2761). Computational resources were provided by the National Energy Research Scientific Computing Center, a Department of Energy Office of Science User Facility supported by the Office of Science of the US Department of Energy under contract No. DE-AC02-05CH11231, and the Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation grant No. ACI-1548562. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHR01GM125063
Office of Naval Research (ONR)N00014-16-1-2761
Department of Energy (DOE)DE-AC02-05CH11231
NSFACI-1548562
Issue or Number:12
Record Number:CaltechAUTHORS:20200304-160026575
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200304-160026575
Official Citation:Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon. Michiel J. M. Niesen, Matthew H. Zimmer, and Thomas F. Miller III. Journal of the American Chemical Society 2020 142 (12), 5449-5460; DOI: 10.1021/jacs.9b07820
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101716
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Mar 2020 00:05
Last Modified:25 Mar 2020 17:12

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