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Determinants of Multispanning Membrane Protein Integration Mediated by the Sec Translocon

Van Lehn, Reid C. and Zhang, Bin and Miller, Thomas F., III (2016) Determinants of Multispanning Membrane Protein Integration Mediated by the Sec Translocon. Biophysical Journal, 110 (3). 56A-57A. ISSN 0006-3495.

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Multispanning membrane proteins - i.e., proteins with multiple transmembrane domains that thread back-and-forth across the cell membrane - are essential for cellular functions that include signal transduction, material transport, and energy conversion. Performing these functions requires the proteins to integrate within the membrane in the correct topology, or the overall orientation of the protein relative to the membrane. The integration of most proteins proceeds via the Sec translocon, a conserved protein-conducting channel that allows a nascent protein chain to access the membrane while being fed into the channel during translation. Previous studies have established that the Sec-facilitated integration of single-spanning proteins depends on factors including nascent chain hydrophobicity and charge; however, the extent to which these properties influence the integration and topology of multispanning proteins is less clear. Here, we use coarse-grained simulations to investigate the Sec-facilitated membrane integration of multispanning proteins on realistic biological timescales. We employ a simulation model that enables access to a timescale of minutes while retaining sufficient chemical accuracy to capture the forces that drive membrane integration. This study focuses on understanding two experimental observations: first, the finding that the protein EmrE exhibits two possible topologies in a 1:1 stoichiometry; and second, the finding that some marginally hydrophobic domains efficiently integrate into the membrane as part of a multispanning protein, despite inefficiently integrating as a single-spanning protein. This work provides mechanistic explanations for these observations, leading to insight into the sequence-level determinants of multispanning membrane protein integration and topology (1).

Item Type:Article
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Van Lehn, Reid C.0000-0003-4885-6599
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2016 Biophysical Society. Published by Elsevier Inc.
Record Number:CaltechAUTHORS:20160603-155727136
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Official Citation:Reid C. Van Lehn, Bin Zhang, Thomas F. Miller III, Determinants of Multispanning Membrane Protein Integration Mediated by the Sec Translocon, Biophysical Journal, Volume 110, Issue 3, Supplement 1, 16 February 2016, Pages 56a-57a, ISSN 0006-3495, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67665
Deposited By: Tony Diaz
Deposited On:04 Jun 2016 17:33
Last Modified:17 Apr 2017 23:09

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