核苷酸交换因子Trio的N端Dbl同源结构域的核磁共振结构与诱变

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

作者信息

Liu X, Wang H, Eberstadt M, Schnuchel A, Olejniczak E T, Meadows R P, Schkeryantz J M, Janowick D A, Harlan J E, Harris E A, Staunton D E, Fesik S W

机构信息

Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.

出版信息

Cell. 1998 Oct 16;95(2):269-77. doi: 10.1016/s0092-8674(00)81757-2.

DOI:10.1016/s0092-8674(00)81757-2

PMID:9790533

Abstract

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 a helices. In addition, we have discovered a unique capability of the PH domain to enhance nucleotide exchange in DH domain-containing proteins.

摘要

Rho家族GTP酶的鸟嘌呤核苷酸交换因子包含一个负责催化作用的Dbl同源（DH）结构域和一个功能未知的普列克底物蛋白同源（PH）结构域。在此，我们描述了Trio的N端DH结构域的溶液结构，该结构域催化Rac1的核苷酸交换。与其他交换因子相比，这个全α螺旋蛋白具有非常不同的结构。基于定点诱变，确定了DH结构域的功能重要残基。它们都高度保守，且位于两条α螺旋上彼此靠近的位置。此外，我们还发现了PH结构域增强含DH结构域蛋白中核苷酸交换的独特能力。