Sgt1-Skp1 复合物的晶体结构：Hsp90 与 SCF E3 泛素连接酶和动粒之间的联系。
The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores.
机构信息
Institute of Structural and Molecular Biology, University College London and Birkbeck, Biological Sciences, Malet Street, London, WC1E 7HX, UK.
Institute of Structural and Molecular Biology, University College London and Birkbeck, Division of Biosciences, Darwin Building, Gower Street, London, WC1E 6BT, UK.
出版信息
Sci Rep. 2017 Jan 31;7:41626. doi: 10.1038/srep41626.
The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans. Dimerization of yeast Sgt1 occurs via an insertion that is absent from monomeric human Sgt1. We identify point mutations that disrupt dimerization and Skp1 binding in vitro and find that the interaction with Skp1 is an essential function of Sgt1 in yeast. Our data provide a structural rationale for understanding the phenotypes of temperature-sensitive Sgt1 mutants and for linking Skp1-associated proteins to Hsp90-dependent pathways.
必需共伴侣 Sgt1 将 Hsp90 伴侣活性募集到一系列细胞因子，包括真核生物中的 SCF E3 泛素连接酶和着丝粒。在这些途径中， Sgt1 与 Skp1 相互作用， Skp1 是一种与含有 F-box 基序的蛋白质异二聚化的小蛋白。我们已经确定了酿酒酵母 Sgt1 和 Skp1 的相互作用结构域的晶体结构，分辨率为 2.8 Å，并在全长蛋白的溶液环境中验证了界面。 Skp1 的 BTB/POZ 结构域通过其 TPR 结构域的凹面与 Sgt1 结合，使用的残基在人类中是保守的。酵母 Sgt1 的二聚化通过插入一个单体人 Sgt1 中不存在的插入片段发生。我们鉴定了破坏体外二聚化和 Skp1 结合的点突变，并发现与 Skp1 的相互作用是 Sgt1 在酵母中的必需功能。我们的数据为理解温度敏感 Sgt1 突变体的表型以及将 Skp1 相关蛋白与 Hsp90 依赖性途径联系起来提供了结构基础。
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