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Published December 12, 2013 | Supplemental Material + Accepted Version
Journal Article Open

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


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.

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.

Attached Files

Accepted Version - nihms540393.pdf

Supplemental Material - mmc1.pdf


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