Journal article

Structures of the cIAP2 RING Domain Reveal Conformational Changes Associated with Ubiquitin-conjugating Enzyme (E2) Recruitment

Peter D Mace, Katrin Linke, Rebecca Feltham, Frances-Rose Schumacher, Clyde A Smith, David L Vaux, John Silke, Catherine L Day

J. Biol. Chem. | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2008

Abstract

Inhibitor of apoptosis (IAP) proteins are key negative regulators of cell death that are highly expressed in many cancers. Cell death caused by antagonists that bind to IAP proteins is associated with their ubiquitylation and degradation. The RING domain at the C terminus of IAP proteins is pivotal. Here we report the crystal structures of the cIAP2 RING domain homodimer alone, and bound to the ubiquitin-conjugating (E2) enzyme UbcH5b. These structures show that small changes in the RING domain accompany E2 binding. By mutating residues at the E2-binding surface, we show that autoubiquitylation is required for regulation of IAP abundance. Dimer formation is also critical, and mutation of a s..

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Grants

Funding Acknowledgements

This work was supported by the Marsden Fund (New Zealand), the National Health and Medical Research Council (Australia), and the Leukemia and Lymphoma Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.A recipient of a Health Sciences Career Development Award (University of Otago).