2DX1

Crystal structure of RhoGEF protein Asef

2DX1 の概要

• エントリーDOI: 10.2210/pdb2dx1/pdb
• 分子名称: Rho guanine nucleotide exchange factor 4 (2 entities in total)
• 機能のキーワード: rho-gef, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 3: Cytoplasm: Q9NR80
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55623.78

構造登録者

Murayama, K.,Kato-Murayama, M.,Terada, T.,Shirouzu, M.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2006-08-22, 公開日: 2007-01-02, 最終更新日: 2024-10-23)

主引用文献

Murayama, K.,Shirouzu, M.,Kawasaki, Y.,Kato-Murayama, M.,Hanawa-Suetsugu, K.,Sakamoto, A.,Katsura, Y.,Suenaga, A.,Toyama, M.,Terada, T.,Taiji, M.,Akiyama, T.,Yokoyama, S.
Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism
J.Biol.Chem., 282:4238-4242, 2007

PubMed Abstract: The Rac-specific guanine nucleotide exchange factor (GEF) Asef is activated by binding to the tumor suppressor adenomatous polyposis coli mutant, which is found in sporadic and familial colorectal tumors. This activated Asef is involved in the migration of colorectal tumor cells. The GEFs for Rho family GTPases contain the Dbl homology (DH) domain and the pleckstrin homology (PH) domain. When Asef is in the resting state, the GEF activity of the DH-PH module is intramolecularly inhibited by an unidentified mechanism. Asef has a Src homology 3 (SH3) domain in addition to the DH-PH module. In the present study, the three-dimensional structure of Asef was solved in its autoinhibited state. The crystal structure revealed that the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site. Furthermore, the RT-loop and the C-terminal region of the SH3 domain interact with the DH domain in a manner completely different from those for the canonical binding to a polyproline-peptide motif. These results demonstrate that the blocking of the Rac-binding site by the SH3 domain is essential for Asef autoinhibition. This may be a common mechanism in other proteins that possess an SH3 domain adjacent to a DH-PH module.

PubMed: 17190834
DOI: 10.1074/jbc.C600234200

実験手法

X-RAY DIFFRACTION (2.36 Å)