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The structural basis of the activation of Ras by Sos

Author

Listed:
  • P. Ann Boriack-Sjodin

    (Laboratories of Molecular Biophysics)

  • S. Mariana Margarit

    (State University of New York at Stony Brook)

  • Dafna Bar-Sagi

    (State University of New York at Stony Brook)

  • John Kuriyan

    (Laboratories of Molecular Biophysics
    Howard Hughes Medical Institute, The Rockefeller University)

Abstract

The crystal structure of human H-Ras complexed with the Ras guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 Å resolution. The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. First, the insertion into Ras of an α-helix from Sos results in the displacement of the Switch 1 region of Ras, opening up the nucleotide-binding site. Second, side chains presented by this helix and by a distorted conformation of the Switch 2 region of Ras alter the chemical environment of the binding site for the phosphate groups of the nucleotide and the associated magnesium ion, so that their binding is no longer favoured. Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras–Sos complex adopts a structure that allows nucleotide release and rebinding.

Suggested Citation

  • P. Ann Boriack-Sjodin & S. Mariana Margarit & Dafna Bar-Sagi & John Kuriyan, 1998. "The structural basis of the activation of Ras by Sos," Nature, Nature, vol. 394(6691), pages 337-343, July.
  • Handle: RePEc:nat:nature:v:394:y:1998:i:6691:d:10.1038_28548
    DOI: 10.1038/28548
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    Cited by:

    1. Abhijeet Kapoor & Alex Travesset, 2014. "Mechanism of the Exchange Reaction in HRAS from Multiscale Modeling," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-12, October.
    2. Teklab Gebregiworgis & Yoshihito Kano & Jonathan St-Germain & Nikolina Radulovich & Molly L. Udaskin & Ahmet Mentes & Richard Huang & Betty P. K. Poon & Wenguang He & Ivette Valencia-Sama & Claire M. , 2021. "The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Baptiste Fischer & Tomasz Uchański & Aidana Sheryazdanova & Simon Gonzalez & Alexander N. Volkov & Elke Brosens & Thomas Zögg & Valentina Kalichuk & Steven Ballet & Wim Versées & Anna A. Sablina & Els, 2024. "Allosteric nanobodies to study the interactions between SOS1 and RAS," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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