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

Rai, Amrita, Bleimling, Nathalie, Vetter, Ingrid R., Goody, Roger S.·2020·Nature Communications
DOI 10.1038/s41467-020-17792-3PMC PMC7442826
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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.

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Metadata

Authors
Rai, A., Bleimling, N., Vetter, I. R., & Goody, R. S.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-08-21
Volume
11
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-020-17792-3
PMC
PMC7442826
Cited by
34
References
0
Language
en
Licence
Funders
Deutsche Forschungsgemeinschaft (GO 284/10-1)

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