Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A

Journal of Biomolecular NMR - Tập 51 - Trang 185-190 - 2011
Alexander Lemak1, Adelinda Yee1, Irina Bezsonova2, Sirano Dhe-Paganon3,4, Cheryl H. Arrowsmith1,3
1Ontario Cancer Institute, Campbell Family Cancer Research Institute and Department of Medical Biophysics, University of Toronto, and Northeast Structural Genomics Consortium, Toronto, Canada
2Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, USA
3Structural Genomics Consortium, University of Toronto, Toronto, Canada
4Department of Physiology, University of Toronto, Toronto, Canada

Tóm tắt

Ube3A (also referred to as E6AP for E6 Associated Protein) is a E3 ubiquitin-protein ligase implicated in the development of Angelman syndrome by controlling degradation of synaptic protein Arc and oncogenic papilloma virus infection by controlling degradation of p53. This article describe the solution NMR structure of the conserved N-terminal domain of human Ube3A (residues 24-87) that contains two residues (Cys44 and Arg62) found to be mutated in patients with Angelman syndrome. The structure of this domain adopts a novel Zn-binding fold we called AZUL (Amino-terminal Zn-finger of Ube3a Ligase). The AZUL domain has a helix-loop-helix architecture with a Zn ion coordinated by four Cys residues arranged in Cys-X4-Cys-X4-Cys-X28-Cys motif. Three of the Zn-bound residues are located in a 23-residue long and well structured loop that connects two α-helicies.

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