A structural ensemble of a ribosome–nascent chain complex during cotranslational protein folding

Cabrita, L. D. et al. (2016) A structural ensemble of a ribosome–nascent chain complex during cotranslational protein folding. Nature Structural and Molecular Biology, 23(4), pp. 278-285. (doi:10.1038/nsmb.3182) (PMID:26926436)

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Although detailed pictures of ribosome structures are emerging, little is known about the structural and cotranslational folding properties of nascent polypeptide chains at the atomic level. Here we used solution-state NMR spectroscopy to define a structural ensemble of a ribosome–nascent chain complex (RNC) formed during protein biosynthesis in Escherichia coli, in which a pair of immunoglobulin-like domains adopts a folded N-terminal domain (FLN5) and a disordered but compact C-terminal domain (FLN6). To study how FLN5 acquires its native structure cotranslationally, we progressively shortened the RNC constructs. We found that the ribosome modulates the folding process, because the complete sequence of FLN5 emerged well beyond the tunnel before acquiring native structure, whereas FLN5 in isolation folded spontaneously, even when truncated. This finding suggests that regulating structure acquisition during biosynthesis can reduce the probability of misfolding, particularly of homologous domains.

Item Type:Articles
Additional Information:We thank J. Kirkpatrick for NMR technical assistance and useful discussions and B. Bukau (Ruprecht-Karls-Universität Heidelberg) for the kind gift of the anti-SecM antibody. J.C. acknowledges the use of the Biomolecular NMR Facility, University College London, and thanks T. Frenkiel and G. Kelly of the Medical Research Council Biomedical NMR Centre at the Crick Institute, London for the use of the facility. J.C. and T.W. acknowledge the use of the Advanced Research Computing High End Resource (ARCHER) UK National supercomputing service (http://www.archer.ac.uk/). L.D.C. is supported by the Wellcome Trust and by an Alpha-1 Foundation grant. A.L.R. is supported as a National Health and Medical Research Council (Australia) C.J. Martin Fellow. T.W. is supported as an European Molecular Biology Organization Long-Term Fellow and is also supported by the Wellcome Trust. The work of C.M.D. and M.V. is supported by a Wellcome Trust Programme Grant (094425/Z/10/Z to C.M.D. and M.V.). This work was supported by a Biotechnology and Biochemical Sciences Research Council New Investigators Award (BBG0156511 to J.C.) and a Wellcome Trust Investigator Award (097806/Z/11/Z to J.C.).
Glasgow Author(s) Enlighten ID:Woolhead, Professor Cheryl
Authors: Cabrita, L. D., Cassaignau, A. M.E., Launay, H. M.M., Waudby, C. A., Wlodarski, T., Camilloni, C., Karyadi, M.-E., Robertson, A. L., Wang, X., Wentink, A. S., Goodsell, L. S., Woolhead, C., Vendruscolo, M., Dobson, C. M., and Christodoulou, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Nature Structural and Molecular Biology
Publisher:Nature Publishing Group
ISSN (Online):1545-9985
Published Online:29 February 2016

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