6ZSH

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

Summary for 6ZSH

• Entry DOI: 10.2210/pdb6zsh/pdb
• Descriptor: EH domain-binding protein 1 (3 entities in total)
• Functional Keywords: rab gtpase, ehbp1, bmerb domain, ch domain, endocytosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 51363.13

Authors

Rai, A.,Bleimling, N.,Vetter, I.R.,Goody, R.S. (deposition date: 2020-07-15, release date: 2020-09-02, Last modification date: 2024-01-31)

Primary citation

Rai, A.,Bleimling, N.,Vetter, I.R.,Goody, R.S.
The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members.
Nat Commun, 11:4187-4187, 2020

PubMed 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.

PubMed: 32826901
DOI: 10.1038/s41467-020-17792-3

Experimental method

X-RAY DIFFRACTION (2.2 Å)