Two high-resolution structures of the human E3 ubiquitin ligase Siah1.

Vadim Rimsa, Thomas C Eadsforth, William N Hunter
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引用次数: 10

Abstract

Siah1 is an E3 ubiquitin ligase that contributes to proteasome-mediated degradation of multiple targets in key cellular processes and which shows promise as a therapeutic target in oncology. Structures of a truncated Siah1 bound to peptide-based inhibitors have been reported. Here, new crystallization conditions have allowed the determination of a construct encompassing dual zinc-finger subdomains and substrate-binding domains at significantly higher resolution. Although the crystals appear isomorphous, two structures present distinct states in which the spatial orientation of one zinc-finger subdomain differs with respect to the rest of the dimeric protein. Such a difference, which is indicative of conformational freedom, infers potential biological relevance related to recognition of binding partners. The crystallization conditions and improved models of Siah1 may aid future studies investigating Siah1-ligand complexes.

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人E3泛素连接酶Siah1的两个高分辨率结构。
Siah1是一种E3泛素连接酶,有助于蛋白酶体介导的关键细胞过程中多个靶标的降解,并有望成为肿瘤治疗靶标。一个截断的Siah1结合肽基抑制剂的结构已经被报道。在这里,新的结晶条件允许以更高的分辨率确定包含双锌指亚结构域和底物结合结构域的结构体。虽然晶体看起来是同构的,但两种结构呈现出不同的状态,其中一个锌指亚结构域的空间取向与二聚体蛋白的其余部分不同。这种差异表明构象自由,推断出与结合伴侣识别相关的潜在生物学相关性。Siah1的结晶条件和改进的模型可能有助于进一步研究Siah1配体复合物。
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期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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