4H6Y

Crystal structure of the DH-PH-PH domain of FARP1

Summary for 4H6Y

• Entry DOI: 10.2210/pdb4h6y/pdb
• Related: 4GZU
• Descriptor: FERM, RhoGEF and pleckstrin domain-containing protein 1 (1 entity in total)
• Functional Keywords: farp1, dh-ph, gef, guanine nucleotide exchange factor, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q9Y4F1
• Total number of polymer chains: 2
• Total formula weight: 115839.84

Authors

He, X.,Zhang, X. (deposition date: 2012-09-19, release date: 2013-03-13, Last modification date: 2024-02-28)

Primary citation

He, X.,Kuo, Y.C.,Rosche, T.J.,Zhang, X.
Structural Basis for Autoinhibition of the Guanine Nucleotide Exchange Factor FARP2.
Structure, 21:355-364, 2013

PubMed 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.

PubMed: 23375260
DOI: 10.1016/j.str.2013.01.001

Experimental method

X-RAY DIFFRACTION (4.09 Å)