Article
Nature 427, 215-221 (15 January 2004) | doi:10.1038/nature02250; Received 25 August 2003; Accepted 25 November 2003
Substrate twinning activates the signal recognition particle and its receptor
Pascal F. Egea1, Shu-ou Shan1,2, Johanna Napetschnig1, David F. Savage1, Peter Walter1,2 and Robert M. Stroud1
- Department of Biochemistry and Biophysics, University of California at San Francisco, California 94143-2240, USA
- Howard Hughes Medical Institute, San Francisco, California 94143, USA
Correspondence to: Pascal F. Egea1Robert M. Stroud1
Email: stroud@msg.ucsf.edu
Email: pascal@msg.ucsf.edu
Coordinates for the FtsY–Ffh heterodimer complex bound to GMPPCP have been deposited in the Protein Data Bank under accession code 1RJ9.
Abstract
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
GTPase twins in the SRP familyNature Structural & Molecular Biology News and Views (01 Feb 2004)
On the beaten pathwayNature News and Views (17 Feb 1994)
See all 3 matches for News And ViewsRESEARCH
RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particleNature Structural & Molecular Biology Article (01 Dec 2005)
Evidence for a novel GTPase priming step in the SRP protein targeting pathwayThe EMBO Journal Article (03 Dec 2001)
See all 26 matches for Research