PDBsum entry 4gzu

Signaling protein

PDB id: 4gzu

Contents

Protein chains

436 a.a.

Waters ×19

PDB id:

4gzu

Name:

Signaling protein

Title:

Crystal structure of the dh-ph-ph domain of farp2

Structure:

Ferm, rhogef and pleckstrin domain-containing protein 2. Chain: a, b. Synonym: ferm domain including rhogef, fir. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: farp2, kiaa0793. Expressed in: escherichia coli. Expression_system_taxid: 469008. Protease site

Resolution:

3.20Å R-factor: 0.235 R-free: 0.278

Authors:

X.He,X.Zhang

Key ref:

X.He et al. (2013). Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2. Structure, 21, 355-364. PubMed id: 23375260 DOI: 10.1016/j.str.2013.01.001

Date:

06-Sep-12 Release date: 13-Mar-13

Protein chains

Q91VS8  (FARP2_MOUSE) -  FERM, ARHGEF and pleckstrin domain-containing protein 2 from Mus musculus

Seq: 1065 a.a.

Struc: 436 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.str.2013.01.001

Structure 21:355-364 (2013)

PubMed id: 23375260

Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2.

X.He, Y.C.Kuo, T.J.Rosche, X.Zhang.

ABSTRACT

FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a 4.1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis. How the GEF activity of FARP2 is regulated remained poorly understood. We have determined the crystal structures of the catalytic DH domain and the DH-PH-PH domains of FARP2. The structures reveal an auto-inhibited conformation in which the GEF substrate-binding site is blocked collectively by the last helix in the DH domain and the two PH domains. This conformation is stabilized by multiple interactions among the domains and two well-structured inter-domain linkers. Our cell-based activity assays confirm the suppression of the FARP2 GEF activity by these auto-inhibitory elements.