PDBsum entry 6zsh

Endocytosis

PDB id: 6zsh

Contents

Protein chains

92 a.a.

108 a.a.

82 a.a.

Waters ×130

PDB id:

6zsh

Name:

Endocytosis

Title:

The mechanism of activation of the actin binding protein ehbp1 by rab8 family members

Structure:

Eh domain-binding protein 1. Chain: a, c. Engineered: yes. Eh domain-binding protein 1. Chain: b, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ehbp1, kiaa0903, nacsin. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.180 R-free: 0.230

Authors:

A.Rai,N.Bleimling,I.R.Vetter,R.S.Goody

Key ref:

A.Rai et al. (2020). The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members. Nat Commun, 11, 4187. PubMed id: 32826901 DOI: 10.1038/s41467-020-17792-3

Date:

15-Jul-20 Release date: 02-Sep-20

Protein chain

Q8NDI1  (EHBP1_HUMAN) -  EH domain-binding protein 1 from Homo sapiens

Seq: 1231 a.a.

Struc: 92 a.a.

Protein chains

Q8NDI1  (EHBP1_HUMAN) -  EH domain-binding protein 1 from Homo sapiens

Seq: 1231 a.a.

Struc: 108 a.a.

Protein chain

Q8NDI1  (EHBP1_HUMAN) -  EH domain-binding protein 1 from Homo sapiens

Seq: 1231 a.a.

Struc: 82 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

DOI no: 10.1038/s41467-020-17792-3

Nat Commun 11:4187 (2020)

PubMed id: 32826901

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

A.Rai, N.Bleimling, I.R.Vetter, R.S.Goody.

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.