3JV3

Structure of SH3E-DH unit of murine intersectin-1L

3JV3 の概要

• エントリーDOI: 10.2210/pdb3jv3/pdb
• 分子名称: Intersectin-1 (2 entities in total)
• 機能のキーワード: sh3 domain, dh domain, guanine nucleotide exchange factor, autoinhibition, domain-swapped, cell junction, cell projection, endocytosis, membrane, phosphoprotein, synapse, synaptosome, protein binding
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Endomembrane system : Q9Z0R4
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65443.48

構造登録者

Ahmad, K.F. (登録日: 2009-09-15, 公開日: 2010-07-14, 最終更新日: 2024-02-21)

主引用文献

Ahmad, K.F.,Lim, W.A.
The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.
Plos One, 5:e11291-e11291, 2010

PubMed Abstract: Intersectin-1L is a member of the Dbl homology (DH) domain guanine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Intersectin-1L is a GEF that is specific for Cdc42. It plays an important role in endocytosis, and is regulated by several partners including the actin regulator N-WASP. Intact intersectin-1L shows low Cdc42 exchange activity, although the isolated catalytic DH domain shows high activity. This finding suggests that the molecule is autoinhibited. To investigate the mechanism of autoinhibition we have constructed a series of domain deletions. We find that the five SH3 domains of intersectin are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. This SH3 domain appears to primarily interact with the DH domain. We have determined the crystal structure of the SH3(E)-DH domain construct, which shows a domain swapped arrangement in which the SH3 from one monomer interacts with the DH domain of the other monomer. Analytical ultracentrifugation and gel filtration, however, show that under biochemical concentrations, the construct is fully monomeric. Thus we propose that the actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction. We propose a model in which this intramolecular interaction may block or distort the GTPase binding region of the DH domain.

PubMed: 20585582
DOI: 10.1371/journal.pone.0011291

実験手法

X-RAY DIFFRACTION (2.4 Å)