Ral-GppNHp和Ral-GDP的晶体结构揭示了Ras和Rap中也存在的两个结合位点。

Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that are also present in Ras and Rap.

作者信息

Nicely Nathan I, Kosak Justin, de Serrano Vesna, Mattos Carla

机构信息

Department of Molecular and Structural Biochemistry, 128 Polk Hall-CB 7622, North Carolina State University, Raleigh, NC 27695, USA.

出版信息

Structure. 2004 Nov;12(11):2025-36. doi: 10.1016/j.str.2004.08.011.

DOI:10.1016/j.str.2004.08.011

PMID:15530367

Abstract

RalA is a GTPase with effectors such as Sec5 and Exo84 in the exocyst complex and RalBP1, a GAP for Rho proteins. We report the crystal structures of Ral-GppNHp and Ral-GDP. Disordered switch I and switch II, located away from crystal contacts, are observed in one of the molecules in the asymmetric unit of the Ral-GppNHp structure. In the other molecule in the asymmetric unit, a second Mg(2+) ion is bound to the GppNHp gamma-phosphate in an environment in which switch I is pulled away from the nucleotide and switch II is found in a tight beta turn. Clustering of conserved residues on the surface of Ral-GppNHp identifies two putative sites for protein-protein interaction. One site is adjacent to switch I. The other is modulated by switch II and is obstructed in Ral-GDP. The Ral structures are discussed in the context of the published structures of the Ral/Sec5 complex, Ras, and Rap.

摘要

RalA是一种GTP酶，其效应分子包括外被体复合物中的Sec5和Exo84以及Rho蛋白的GAP（GTP酶激活蛋白）RalBP1。我们报道了Ral-GppNHp和Ral-GDP的晶体结构。在Ral-GppNHp结构不对称单元中的一个分子中，观察到远离晶体接触的无序开关I和开关II。在不对称单元中的另一个分子中，第二个Mg(2+)离子在开关I远离核苷酸且开关II呈紧密β转角的环境中与GppNHpγ-磷酸结合。Ral-GppNHp表面保守残基的聚集确定了两个假定的蛋白质-蛋白质相互作用位点。一个位点与开关I相邻。另一个位点受开关II调节，在Ral-GDP中被阻断。将结合已发表的Ral/Sec5复合物、Ras和Rap的结构来讨论Ral的结构。