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Structural basis of signal sequence surveillance and selection by the SRP–FtsY complex

von Loeffelholz, Ottilie and Knoops, Kèvin and Ariosa, Aileen and Zhang, Xin and Karuppasamy, Manikandan and Huard, Karine and Schoehn, Guy and Berger, Imre and Shan, Shu-ou and Schaffitzel, Christiane (2013) Structural basis of signal sequence surveillance and selection by the SRP–FtsY complex. Nature Structural & Molecular Biology, 20 (5). pp. 604-610. ISSN 1545-9985. PMCID PMC3874396.

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Signal-recognition particle (SRP)-dependent targeting of translating ribosomes to membranes is a multistep quality-control process. Ribosomes that are translating weakly hydrophobic signal sequences can be rejected from the targeting reaction even after they are bound to the SRP. Here we show that the early complex, formed by Escherichia coli SRP and its receptor FtsY with ribosomes translating the incorrect cargo EspP, is unstable and rearranges inefficiently into subsequent conformational states, such that FtsY dissociation is favored over successful targeting. The N-terminal extension of EspP is responsible for these defects in the early targeting complex. The cryo-electron microscopy structure of this 'false' early complex with EspP revealed an ordered M domain of SRP protein Ffh making two ribosomal contacts, and the NG domains of Ffh and FtsY forming a distorted, flexible heterodimer. Our results provide a structural basis for SRP-mediated signal-sequence selection during recruitment of the SRP receptor.

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Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. Received 8 November 2012; accepted 21 February 2013; published online 7 April 2013. We thank T. Shaikh for advice with Spider refinement, P. Penczek for assistance with SPARX, M. Bacia for excellent technical assistance and members of the protein expression facility at European Molecular Biology Laboratory Heidelberg as well as the Partnership for Structural Biology in Grenoble for support. The Polara microscope is part of the Structural Biology and Dynamics Groupement d’intérêt scientifique–Infrastrutures en Biologie Sante et Agronomie platform of the Institut de Biologie Structurale. C.S. acknowledges support by the Agence Nationale de la Recherche (ANR-09-JCJC-0044), the region Rhône-Alpes (CIBLE_1976) and the European Research Council Starting grant (project 281331). K.K. was supported by a postdoctoral European Molecular Biology Organization fellowship. We thank I. Saraogi in the Shan laboratory for sharing unpublished results and for critical reading of the manuscript. S.S. is supported by US National Institutes of Health grant R01 GM078024, and the Fellowship for science and engineering from the David and Lucile Packard foundation. A.A. was supported by the US National Institute of General Medical Sciences Ruth L. Kirschstein National Research Service Award (F31GM095294) and the National Institutes of Health National Research Service Award Training grant 5T32GM07616. X.Z. is supported by the Howard Hughes Medical Institute Fellowship of the Helen Hay Whitney Foundation. Author Contributions: C.S., I.B., X.Z. and S.S. designed experiments; C.S., K.H., O.v.L., A.A. and X.Z. prepared samples; A.A. and X.Z. carried out biochemical experiments; K.K., G.S. and M.K. performed the electron microscopy; O.v.L., M.K. and C.S. performed image analysis and model building; C.S., O.v.L., A.A., X.Z. and S.S. prepared the manuscript.
Funding AgencyGrant Number
Agence Nationale de la Recherche (ANR)ANR-09-JCJC-0044
Region Rhône-AlpesCIBLE_1976
European Research Council (ERC)281331
European Molecular Biology Organization (EMBO)UNSPECIFIED
NIHR01 GM078024
David and Lucile Packard FoundationUNSPECIFIED
NIH Postdoctoral FellowshipF31GM095294
NIH Predoctoral Fellowship5T32GM07616
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Helen Hay Whitney FoundationUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC3874396
Record Number:CaltechAUTHORS:20130625-102457328
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39075
Deposited By: Jason Perez
Deposited On:25 Jun 2013 20:25
Last Modified:03 Oct 2019 05:03

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