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Published January 14, 2004 | Supplemental Material
Journal Article Open

Substrate twinning activates the signal recognition particle and its receptor


Signal sequences target proteins for secretion from cells or for integration into cell membranes. As nascent proteins emerge from the ribosome, signal sequences are recognized by the signal recognition particle (SRP), which subsequently associates with its receptor (SR). In this complex, the SRP and SR stimulate each other's GTPase activity, and GTP hydrolysis ensures unidirectional targeting of cargo through a translocation pore in the membrane. To define the mechanism of reciprocal activation, we determined the 1.9 Å structure of the complex formed between these two GTPases. The two partners form a quasi-two-fold symmetrical heterodimer. Biochemical analysis supports the importance of the extensive interaction surface. Complex formation aligns the two GTP molecules in a symmetrical, composite active site, and the 3′OH groups are essential for association, reciprocal activation and catalysis. This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery.

Additional Information

© 2004 Nature Publishing Group. Received 25 August 2003; Accepted 25 November 2003; Issue Date 15 January 2004. We thank C. Reyes for invaluable contributions to the initial FtsY mutant design and structure determination of T. aquaticus FtsY·GMPPNP, and R. Vale, H. Bourne and N. Bradshaw for comments on the manuscript. We acknowledge K. Slep and L. Rice for discussion and advice, and thank J. Holton and G. Meigg for support during data collection at the Advanced Light Source. D.F.S was supported by a Burroughs-Wellcome Fund graduate fellowship. S.S. is supported by a Damon Runyan/Walter Winchell Cancer research fellowship. This work was supported by NIH grants to R.M.S. and P.W. P.W is an Investigator of the Howard Hughes Medical Institute. The authors declare that they have no competing financial interests.

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