title: 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.
authors: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
authors: Vadim
authors: V
authors: Rimsa
authors: Thomas C
authors: TC
authors: Eadsforth
authors: William N
authors: WN
authors: Hunter
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D011994:Recombinant Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex
keywords: E3 ubiquitin ligase; seven-in-absentia homologue 1 (Siah1); zinc finger