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Coarse-Grained Modeling of Membrane Protein Integration via the Sec Translocon

Niesen, Michiel J. M. and Wang, Connie Y. and Miller, Thomas F., III (2016) Coarse-Grained Modeling of Membrane Protein Integration via the Sec Translocon. Biophysical Journal, 110 (3). 56A. ISSN 0006-3495. doi:10.1016/j.bpj.2015.11.371. https://resolver.caltech.edu/CaltechAUTHORS:20160603-155356794

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Abstract

Integration into the cell membrane is a key step in the biogenesis of membrane proteins. Membrane protein integration takes place at the Sec translocon and typically occurs during the ribosomal translation of the protein sequence. The study of Sec-facilitated membrane protein integration is difficult due to the roles of long-timescale dynamics and ribosomal translation. We present a coarse-grained (CG) simulation approach that is capable of reaching the experimentally relevant (i.e., minute) timescales, while retaining the level of detail required to capture amino-acid sequence level properties. The CG model enables direct simulation of co-translational integration at the Sec translocon and analysis of the resulting trajectories provides mechanistic explanations for observed experimental data. We demonstrate the use of the developed CG model to investigate the experimentally observed forces exerted on a nascent protein during co-translational membrane integration. It has been observed experimentally that the force exerted on the nascent protein depends on various factors, including the number of amino-acids that have been translated, nascent protein charge, and nascent protein hydrophobicity. Importantly, the CG model captures the effect of these factors on the force exerted on the nascent protein, enabling further analysis of the calculated trajectories to determine how the observed forces relate to the underlying physical process.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bpj.2015.11.371DOIArticle
http://www.sciencedirect.com/science/article/pii/S0006349515015544PublisherArticle
ORCID:
AuthorORCID
Niesen, Michiel J. M.0000-0002-9255-6203
Wang, Connie Y.0000-0003-2971-3971
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2016 Biophysical Society. Published by Elsevier Inc.
Issue or Number:3
DOI:10.1016/j.bpj.2015.11.371
Record Number:CaltechAUTHORS:20160603-155356794
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160603-155356794
Official Citation:Michiel J.M. Niesen, Connie Y. Wang, Thomas F. Miller III, Coarse-Grained Modeling of Membrane Protein Integration via the Sec Translocon, Biophysical Journal, Volume 110, Issue 3, Supplement 1, 16 February 2016, Page 56a, ISSN 0006-3495, http://dx.doi.org/10.1016/j.bpj.2015.11.371. (http://www.sciencedirect.com/science/article/pii/S0006349515015544)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67664
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:04 Jun 2016 17:34
Last Modified:11 Nov 2021 03:52

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