NMR structure and mutagenesis of the N-terminal Dbl homology domain of the nucleotide exchange factor trio

被引：155

作者：

Liu, XH

Wang, H

Eberstadt, M

Schnuchel, A

Olejniczak, ET

Meadows, RP

Schkeryantz, JM

Janowick, DA

Harlan, JE

Harris, EAS

Staunton, DE

Fesik, SW ^{[1
]}

机构：

[1] Abbott Labs, Div Pharmaceut Discovery, Abbott Pk, IL 60064 USA

[2] ICOS Corp, Bothell, WA 98021 USA

来源：

CELL | 1998年 / 95卷 / 02期

关键词：

D O I：

10.1016/S0092-8674(00)81757-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Guanine nucleotide exchange factors for the Rho family of GTPases contain a Dbl homology (DH) domain responsible for catalysis and a pleckstrin homology (PH) domain whose function is unknown. Here we describe the solution structure of the N-terminal DH domain of Trio that catalyzes nucleotide exchange for Rac1. The all-alpha-helical protein has a very different structure compared to other exchange factors. Based on site-directed mutagenesis, functionally important residues of the DH domain were identified. They are all highly conserved and reside in close proximity on two alpha helices. In addition, we have discovered a unique capability of the PH domain to enhance nucleotide exchange in DH domain-containing proteins.

引用

页码：269 / 277

页数：9

共 52 条

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