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

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.

SUBMITTER: Rimsa V

PROVIDER: S-EPMC3855715 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Rimsa Vadim V Eadsforth Thomas C TC Hunter William N WN

Acta crystallographica. Section F, Structural biology and crystallization communications 20131128 Pt 12

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 isom ...[more]

PMID: 24316825

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