Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin
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DOI：
10.1016/j.cell.2006.02.020
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发表时间：
2006-03-24
期刊：
影响因子：
64.5
通讯作者：
Schneider, TR
中科院分区：
文献类型：
--
作者：
Penengo, L;Mapelli, M;Schneider, TR
泛素化蛋白与含有泛素结合域 (UBD) 的细胞内蛋白之间的相互作用对于多种细胞过程至关重要。在这里，我们报道 Rabex-5（Rab5 的鸟嘌呤核苷酸交换因子）通过两个独立的 UBD 与 Ub 结合。这些 UBD 决定了 Rabex-5 的许多特性，包括其偶联的单泛素化以及与泛素化 EGFR 的体内相互作用。 Rabex-5 UBD 的结构和生化特征表明，其中一个（MIU，与泛素相互作用的基序）与 Ub 的结合模式与 UIM（泛素相互作用基序）的模式重叠：Ub 相互作用，尽管方向相反，另一个 UBD，RUZ（Rabex-5 泛素结合锌指）与 UIM 的表面结合。 Ub 以 Asp58(Ub) 为中心，与“规范的”基于 Ile44(Ub) 的表面不同。这两个结合表面允许 Ub 同时与不同的 UBD 相互作用，从而为 Ub 介导的信号传导开辟了新的视角。
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation, The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.