1LB1

Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA

1LB1 の概要

• エントリーDOI: 10.2210/pdb1lb1/pdb
• 関連するPDBエントリー: 1FOE 1KI1 1KZ7 1KZG
• 分子名称: Guanine nucleotide exchange factor DBS, Transforming protein RhoA (2 entities in total)
• 機能のキーワード: guanine nucleotide exchange factor, small g-protein, rhoa, dbs, dh domain, ph domain, signaling protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Cytoplasm: Q64096; Cell membrane; Lipid-anchor; Cytoplasmic side: P61586
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 251352.43

構造登録者

Snyder, J.T.,Worthylake, D.K.,Rossman, K.L.,Betts, L.,Pruitt, W.M.,Siderovski, D.P.,Der, C.J.,Sondek, J. (登録日: 2002-04-01, 公開日: 2002-05-29, 最終更新日: 2023-08-16)

主引用文献

Snyder, J.T.,Worthylake, D.K.,Rossman, K.L.,Betts, L.,Pruitt, W.M.,Siderovski, D.P.,Der, C.J.,Sondek, J.
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.
Nat.Struct.Biol., 9:468-475, 2002

PubMed Abstract: Activation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo.

PubMed: 12006984
DOI: 10.1038/nsb796

実験手法

X-RAY DIFFRACTION (2.81 Å)