RalB-RLIP76 复合物揭示了一种新型的 Ral 效应物相互作用模式。
The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction.
机构信息
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
出版信息
Structure. 2010 Aug 11;18(8):985-95. doi: 10.1016/j.str.2010.05.013.
Abstract
RLIP76 (RalBP1) is a multidomain protein that interacts with multiple small G protein families: Ral via a specific binding domain, and Rho and R-Ras via a GTPase activating domain. RLIP76 interacts with endocytosis proteins and has also been shown to behave as a membrane ATPase that transports chemotherapeutic agents from the cell. We have determined the structure of the Ral-binding domain of RLIP76 and show that it comprises a coiled-coil motif. The structure of the RLIP76-RalB complex reveals a novel mode of binding compared to the structures of RalA complexed with the exocyst components Sec5 and Exo84. RLIP76 interacts with both nucleotide-sensitive regions of RalB, and key residues in the interface have been identified using affinity measurements of RalB mutants. Sec5, Exo84, and RLIP76 bind Ral proteins competitively and with similar affinities in vitro.
摘要
RLIP76（RalBP1）是一种具有多个结构域的蛋白质，可与多个小 G 蛋白家族相互作用：通过特定的结合域与 Ral 相互作用，通过 GTP 酶激活结构域与 Rho 和 R-Ras 相互作用。RLIP76 与内吞作用蛋白相互作用，并且还表现为膜 ATP 酶，可将化学治疗剂从细胞中转运出来。我们已经确定了 RLIP76 的 Ral 结合结构域的结构，并表明它由一个卷曲螺旋结构域组成。RLIP76-RalB 复合物的结构揭示了与 RalA 与外泌体成分 Sec5 和 Exo84 形成的复合物的结构相比，一种新的结合模式。RLIP76 与 RalB 的核苷酸敏感区域相互作用，并且使用 RalB 突变体的亲和力测量鉴定了界面中的关键残基。Sec5、Exo84 和 RLIP76 在体外竞争性地与 Ral 蛋白结合，并且具有相似的亲和力。
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