4GZU

Crystal structure of the DH-PH-PH domain of FARP2

4GZU の概要

• エントリーDOI: 10.2210/pdb4gzu/pdb
• 関連するPDBエントリー: 4GYV
• 分子名称: FERM, RhoGEF and pleckstrin domain-containing protein 2 (2 entities in total)
• 機能のキーワード: farp2, dhph, gef, guanine nucleotide exchange factor, signaling protein
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116140.81

構造登録者

He, X.,Zhang, X. (登録日: 2012-09-06, 公開日: 2013-03-13, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.2 Å)