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The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members

Author

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  • Amrita Rai

    (Max Planck Institute of Molecular Physiology)

  • Nathalie Bleimling

    (Max Planck Institute of Molecular Physiology)

  • Ingrid R. Vetter

    (Max Planck Institute of Molecular Physiology)

  • Roger S. Goody

    (Max Planck Institute of Molecular Physiology)

Abstract

EHBP1 is an adaptor protein that regulates vesicular trafficking by recruiting Rab8 family members and Eps15-homology domain-containing proteins 1/2 (EHD1/2). It also links endosomes to the actin cytoskeleton. However, the underlying molecular mechanism of activation of EHBP1 actin-binding activity is unclear. Here, we show that both termini of EHBP1 have membrane targeting potential. EHBP1 associates with PI(3)P, PI(5)P, and phosphatidylserine via its N-terminal C2 domain. We show that in the absence of Rab8 family members, the C-terminal bivalent Mical/EHBP Rab binding (bMERB) domain forms an intramolecular complex with its central calponin homology (CH) domain and auto-inhibits actin binding. Rab8 binding to the bMERB domain relieves this inhibition. We have analyzed the CH:bMERB auto-inhibited complex and the active bMERB:Rab8 complex biochemically and structurally. Together with structure-based mutational studies, this explains how binding of Rab8 frees the CH domain and allows it to interact with the actin cytoskeleton, leading to membrane tubulation.

Suggested Citation

  • Amrita Rai & Nathalie Bleimling & Ingrid R. Vetter & Roger S. Goody, 2020. "The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17792-3
    DOI: 10.1038/s41467-020-17792-3
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    Cited by:

    1. Amrita Rai & Anurag K. Singh & Nathalie Bleimling & Guido Posern & Ingrid R. Vetter & Roger S. Goody, 2022. "Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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