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Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP

Nature Structural Biology volume 6, pages 793–801 (1999)Cite this article

Abstract

Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 Å resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.

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Figure 1: a, Stereoview of the structure of the NG GTPase domain.
Figure 2: The nucleotide-binding site in the GDP structures (G2 and G1), and the apo structure (A1).
Figure 3: Comparison of the GDP-binding interactions in Ffh (G2) with those in Ras (4q21).
Figure 4: Functionally important flexibility in the structures of the NG domain.
Figure 5: Cartoon summarizing the structural consequences of binding of Mg2+GDP and GDP to NG.

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Acknowledgements

We thank J. Richardson of Duke University for an illuminating discussion. This work was begun while D.M.F. was a postdoctoral fellow in the laboratories of P.W. and R.M.S. It was supported by grants to P.W. and R.M.S. from the NIH and by the Herb Boyer Fund and the Biotechnology Program of the University of California. It is based in part on research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), a facility funded by the Department of Energy, Office of Basic Energy Sciences. P.W. is an investigator in the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, 60611, Illinois, USA

    Douglas M. Freymann

  2. Department of Biochemistry and Biophysics, University of California, San Francisco, 94143-0448, California, USA

    Robert J. Keenan, Robert M. Stroud & Peter Walter

  3. Howard Hughes Medical Institute, University of California, San Francisco, 94143-0448, California, USA

    Peter Walter

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Correspondence to Douglas M. Freymann.

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Freymann, D., Keenan, R., Stroud, R. et al. Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP. Nat Struct Mol Biol 6, 793–801 (1999). https://doi.org/10.1038/11572

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