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Structural basis for the molecular evolution of SRP-GTPase activation by protein

Nature Structural & Molecular Biology volume 18, pages 1376–1380 (2011)Cite this article

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Abstract

Small G proteins have key roles in signal transduction pathways. They are switched from the signaling 'on' to the non-signaling 'off' state when GTPase-activating proteins (GAPs) provide a catalytic residue. The ancient signal recognition particle (SRP)-type GTPases form GTP-dependent homo- and heterodimers and deviate from the canonical switch paradigm in that no GAPs have been identified. Here we show that the YlxH protein activates the SRP-GTPase FlhF. The crystal structure of the Bacillus subtilis FlhF–effector complex revealed that the effector does not contribute a catalytic residue but positions the catalytic machinery already present in SRP-GTPases. We provide a general concept that might also apply to the RNA-driven activation of the universally conserved, co-translational protein-targeting machinery comprising the SRP-GTPases Ffh and FtsY. Our study exemplifies the evolutionary transition from RNA- to protein-driven activation in SRP-GTPases and suggests that the current view on SRP-mediated protein targeting is incomplete.

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Figure 1: The SRP-GTPase FlhF is activated by the MinD homolog YlxH.
Figure 2: Structural basis for the activation of FlhF by YlxH.
Figure 3: Mechanism and molecular evolution of SRP-GTPase activation.

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Acknowledgements

This work was supported by the German Research Council SFB638 (I.S.), the Graduiertenkolleg GRK1188 and the interdisciplinary PhD program “Molecular Machines: Mechanisms and Functional Interconnections” of the Land Baden-Württemberg (I.S.). I.S. and E.H. are investigators of the Cluster of Excellence:CellNetworks. We are grateful to A. Hendricks for her excellent technical assistance, U. Pachmayr for her contribution in the beginning of the project and R. Pipkorn (Deutsches Krebsforschungszentrum) for peptide synthesis. We thank J. Kopp and C. Siegmann from the BZH/Cluster of Excellence: CellNetworks crystallization platform for their support and E. Thomson for critical reading of the manuscript. Data collection was performed at ESRF beamline ID14-4 (European Synchrotron Radiation Facility).

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  1. Georg Petzold & Dieter Kressler

    Present address: Present addresses: Research Institute of Molecular Pathology, Vienna, Austria (G.P.); Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland (D.K.).,

  2. Gert Bange and Nico Kümmerer: These authors contributed equally to this work.

Authors and Affiliations

  1. Heidelberg University Biochemistry Center, Heidelberg, Germany

    Gert Bange, Nico Kümmerer, Przemyslaw Grudnik, Robert Lindner, Georg Petzold, Dieter Kressler, Ed Hurt, Klemens Wild & Irmgard Sinning

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Contributions

G.B. and I.S. designed the experiments, analyzed the data and wrote the manuscript. G.B. and N.K. performed the experiments. D.K. and E.H. provided the yeast-two hybrid analysis. P.G. and G.P. contributed to the activation assays. G.B., K.W. and I.S. performed crystallographic analysis. R.L. performed the computational analysis. All authors commented on the manuscript.

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Correspondence to Gert Bange or Irmgard Sinning.

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Bange, G., Kümmerer, N., Grudnik, P. et al. Structural basis for the molecular evolution of SRP-GTPase activation by protein. Nat Struct Mol Biol 18, 1376–1380 (2011). https://doi.org/10.1038/nsmb.2141

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