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Forces on nascent polypeptides during membrane insertion and translocation via the Sec translocon

Niesen, Michiel J. M. and Müller-Lucks, Annika and Hedman, Rickard and von Heijne, Gunnar and Miller, Thomas F., III (2018) Forces on nascent polypeptides during membrane insertion and translocation via the Sec translocon. Biophysical Journal, 115 (10). pp. 1885-1894. ISSN 0006-3495. PMCID PMC6303271. doi:10.1016/j.bpj.2018.10.002.

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During ribosomal translation, nascent polypeptide chains (NCs) undergo a variety of physical processes that determine their fate in the cell. This study utilizes a combination of arrest peptide (AP) experiments and coarse-grained molecular dynamics (CGMD) to measure and elucidate the molecular origins of forces that are exerted on NCs during co-translational membrane insertion and translocation via the Sec translocon. The approach enables deconvolution of force contributions from NC-translocon and NC-ribosome interactions, membrane partitioning, and electrostatic coupling to the membrane potential. In particular, we show that forces due to NC-lipid interactions provide a read-out of conformational changes in the Sec translocon, demonstrating that lateral gate opening only occurs when a sufficiently hydrophobic segment of NC residues reaches the translocon. The combination of experiment and theory introduced here provides a detailed picture of the molecular interactions and conformational changes during ribosomal translation that govern protein biogenesis.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper CentralArticle
Niesen, Michiel J. M.0000-0002-9255-6203
Miller, Thomas F., III0000-0002-1882-5380
Additional Information:© 2018 Biophysical Society. Received 16 August 2018, Accepted 2 October 2018, Available online 10 October 2018. GvH acknowledges support from the Knut and Alice Wallenberg Foundation, the Swedish Cancer Foundation, and the Swedish Research Council. TFM acknowledges 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 (NERSC), a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231 and the Extreme Science and Engineering Discovery Environment (XSEDE) (40), which is supported by National Science Foundation grant number ACI-1548562. Author Contributions: M.J.M.N, T.F.M., and G.v.H. conceived the experiments, M.J.M.N, A.M-L, and R.H. conducted the experiments, All authors analyzed the results and reviewed the manuscript.
Funding AgencyGrant Number
Knut and Alice Wallenberg FoundationUNSPECIFIED
Swedish Cancer FoundationUNSPECIFIED
Swedish Research CouncilUNSPECIFIED
Office of Naval Research (ONR)N00014-16-1-2761
Department of Energy (DOE)DE-AC02-05CH11231
Issue or Number:10
PubMed Central ID:PMC6303271
Record Number:CaltechAUTHORS:20181010-105319720
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Official Citation:Michiel J.M. Niesen, Annika Müller-Lucks, Rickard Hedman, Gunnar von Heijne, Thomas F. Miller, Forces on Nascent Polypeptides during Membrane Insertion and Translocation via the Sec Translocon, Biophysical Journal, Volume 115, Issue 10, 2018, Pages 1885-1894, ISSN 0006-3495, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90226
Deposited By: Tony Diaz
Deposited On:10 Oct 2018 18:01
Last Modified:01 Jun 2023 22:37

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