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The Structural Basis of FtsY Recruitment and GTPase Activation by SRP RNA

Voigts-Hoffmann, Felix and Schmitz, Nikolaus and Shen, Kuang and Shan, Shu-ou and Ataide, Sandro F. and Ban, Nenad (2013) The Structural Basis of FtsY Recruitment and GTPase Activation by SRP RNA. Molecular Cell, 52 (5). pp. 643-654. ISSN 1097-2765. PMCID PMC3910249.

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The universally conserved signal recognition particle (SRP) system mediates the targeting of membrane proteins to the translocon in a multistep process controlled by GTP hydrolysis. Here we present the 2.6 Å crystal structure of the GTPase domains of the E. coli SRP protein (Ffh) and its receptor (FtsY) in complex with the tetraloop and the distal region of SRP-RNA, trapped in the activated state in presence of GDP:AlF_4. The structure reveals the atomic details of FtsY recruitment and, together with biochemical experiments, pinpoints G83 as the key RNA residue that stimulates GTP hydrolysis. Insertion of G83 into the FtsY active site orients a single glutamate residue provided by Ffh (E277), triggering GTP hydrolysis and complex disassembly at the end of the targeting cycle. The complete conservation of the key residues of the SRP-RNA and the SRP protein implies that the suggested chemical mechanism of GTPase activation is applicable across all kingdoms.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Shan, Shu-ou0000-0002-6526-1733
Ban, Nenad0000-0002-9527-210X
Additional Information:© 2013 Elsevier Inc. Received: March 5, 2013. Revised: August 27, 2013. Accepted: October 4, 2013. Published: November 7, 2013. We acknowledge support by the Swiss National Science Foundation (SNSF), the National Center of Excellence in Research (NCCR) Structural Biology program of the SNSF, and European Research Council grant 250071 under the European Community’s Seventh Framework Programme. N.S. was supported by the Boehringer-Ingelheim Fonds. S.S. was supported by NIH grant R01GM078024 and the Packard and Lucile Award in Science and Engineering. We thank Daniel Boehringer and Marc Leibundgut for critical discussions of the manuscript and Stephan Imseng for contributions to the initial stages of the project.
Funding AgencyGrant Number
Swiss National Science Foundation (SNSF)UNSPECIFIED
European Research Council (ERC)250071
Boehringer-Ingelheim FondsUNSPECIFIED
NIHR01 GM078024
David and Lucile Packard FoundationUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC3910249
Record Number:CaltechAUTHORS:20131223-080921779
Persistent URL:
Official Citation:Felix Voigts-Hoffmann, Nikolaus Schmitz, Kuang Shen, Shu-ou Shan, Sandro F. Ataide, Nenad Ban, The Structural Basis of FtsY Recruitment and GTPase Activation by SRP RNA, Molecular Cell, Volume 52, Issue 5, 12 December 2013, Pages 643-654, ISSN 1097-2765, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43131
Deposited By: Ruth Sustaita
Deposited On:23 Dec 2013 16:46
Last Modified:09 Mar 2020 13:18

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