DOCK180 的 SH3 结构域的溶液结构。

Solution structure of the SH3 domain of DOCK180.

机构信息

Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

出版信息

Proteins. 2013 May;81(5):906-10. doi: 10.1002/prot.24236. Epub 2013 Feb 25.

DOI:10.1002/prot.24236

PMID:23239367

Abstract

DOCK180 family proteins are Rho guanine nucleotide exchange factors. DOCK1-5 contains an N-terminal SH3 domain implicated in their autoinhibition. Release of the closed conformation requires the interaction between SH3 and engulfment and cell motility (ELMO). Here, we solved the solution structure of DOCK180 SH3 domain, which shares similar target binding features with the SH3 domain of DOCK2. The conserved N-terminal extension packs with the SH3 core domain and forms a new target binding site distinct from the canonical "PxxP" site. Our results demonstrate that the bidentate target binding mode of DOCK180 SH3 domain might be a general feature in all DOCK proteins.

摘要

DOCK180 家族蛋白是 Rho 鸟苷酸交换因子。DOCK1-5 含有一个 N 端 SH3 结构域，该结构域参与其自身抑制。封闭构象的释放需要 SH3 与吞噬和细胞运动（ELMO）之间的相互作用。在这里，我们解决了 DOCK180 SH3 结构域的溶液结构，该结构域与 DOCK2 的 SH3 结构域具有相似的靶标结合特征。保守的 N 端延伸与 SH3 核心结构域结合，并形成一个与经典“PxxP”结合位点不同的新靶标结合位点。我们的结果表明，DOCK180 SH3 结构域的双位靶标结合模式可能是所有 DOCK 蛋白的一般特征。