Forces on Nascent Polypeptides during Membrane Insertion and Translocation via the Sec Translocon

Niesen, Michiel J. M.; Müller-Lucks, Annika; Hedman, Rickard; von Heijne, Gunnar; Miller, Thomas F.

doi:10.1016/j.bpj.2018.10.002

Title: Forces on Nascent Polypeptides during Membrane Insertion and Translocation via the Sec Translocon

Journal Article · 10 October 2018 · Biophysical Journal

DOI: https://doi.org/10.1016/j.bpj.2018.10.002 · OSTI ID:1543513

Niesen, Michiel J. M. ^[1]; Müller-Lucks, Annika ^[2]; Hedman, Rickard ^[2]; von Heijne, Gunnar ^[2]; Miller, Thomas F. ^[1]

California Inst. of Technology (CalTech), Pasadena, CA (United States)
Stockholm Univ. (Sweden)

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 experiments and coarse-grained molecular dynamics to measure and elucidate the molecular origins of forces that are exerted on NCs during cotranslational 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 readout 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1543513

Journal Information:: Biophysical Journal, Journal Name: Biophysical Journal Journal Issue: 10 Vol. 115; ISSN 0006-3495

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Domain topology, stability, and translation speed determine mechanical force generation on the ribosome Leininger, Sarah E.; Trovato, Fabio; Nissley, Daniel A. Proceedings of the National Academy of Sciences, Vol. 116, Issue 12 https://doi.org/10.1073/pnas.1813003116	journal	March 2019
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