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Substrate twinning activates the signal recognition particle and its receptor

Author

Listed:
  • Pascal F. Egea

    (University of California at San Francisco)

  • Shu-ou Shan

    (University of California at San Francisco
    Howard Hughes Medical Institute)

  • Johanna Napetschnig

    (University of California at San Francisco)

  • David F. Savage

    (University of California at San Francisco)

  • Peter Walter

    (University of California at San Francisco
    Howard Hughes Medical Institute)

  • Robert M. Stroud

    (University of California at San Francisco)

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.

Suggested Citation

  • Pascal F. Egea & Shu-ou Shan & Johanna Napetschnig & David F. Savage & Peter Walter & Robert M. Stroud, 2004. "Substrate twinning activates the signal recognition particle and its receptor," Nature, Nature, vol. 427(6971), pages 215-221, January.
  • Handle: RePEc:nat:nature:v:427:y:2004:i:6971:d:10.1038_nature02250
    DOI: 10.1038/nature02250
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    Cited by:

    1. Pascal F Egea & Hiro Tsuruta & Gladys P de Leon & Johanna Napetschnig & Peter Walter & Robert M Stroud, 2008. "Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane," PLOS ONE, Public Library of Science, vol. 3(11), pages 1-14, November.
    2. Laura Czech & Christopher-Nils Mais & Hanna Kratzat & Pinku Sarmah & Pietro Giammarinaro & Sven-Andreas Freibert & Hanna Folke Esser & Joanna Musial & Otto Berninghausen & Wieland Steinchen & Roland B, 2022. "Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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