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Science 16 January 2004:
Vol. 303. no. 5656, pp. 373 - 377
DOI: 10.1126/science.1090827
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Reports

Heterodimeric GTPase Core of the SRP Targeting Complex

Pamela J. Focia, Irina V. Shepotinovskaya, James A. Seidler, Douglas M. Freymann*

Two structurally homologous guanosine triphosphatase (GTPase) domains interact directly during signal recognition particle (SRP)–mediated cotranslational targeting of proteins to the membrane. The 2.05 angstrom structure of a complex of the NG GTPase domains of Ffh and FtsY reveals a remarkably symmetric heterodimer sequestering a composite active site that contains two bound nucleotides. The structure explains the coordinate activation of the two GTPases. Conformational changes coupled to formation of their extensive interface may function allosterically to signal formation of the targeting complex to the signal-sequence binding site and the translocon. We propose that the complex represents a molecular "latch" and that its disengagement is regulated by completion of assembly of the GTPase active site.

Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.



Note added in proof: A structure of a similar complex of the SRP GTPases in a different crystal form was independently determined and is reported by Egea et al. (36).

* To whom correspondence should be addressed. E-mail: freymann{at}northwestern.edu

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