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Crystal structure of a vFlip-IKK gamma complex: Insights into viral activation of the IKK signalosome

Bagneris, Claire and Ageichik, A.V. and Cronin, Nora and Wallace, Bonnie A. and Collins, M. and Boshoff, C. and Waksman, Gabriel and Barrett, Tracey E. (2008) Crystal structure of a vFlip-IKK gamma complex: Insights into viral activation of the IKK signalosome. Molecular Cell 30 (5), pp. 620-631. ISSN 1097-2765.

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Official URL: http://dx.doi.org/10.1016/j.molcel.2008.04.029

Abstract

Key to the pathogenicity of several viruses is activation of the canonical nuclear factor-κB (NF-κB) transcriptional pathway. Subversion of this tightly regulated mechanism is achieved through the production of host mimetic viral proteins that deregulate the transcription process. One such protein is ks-vFLIP (produced by the Kaposi's sarcoma herpes virus [KSHV]), which associates with IKKγ, an essential component of the IKK complex or signalosome. This interaction renders the canonical NF-κB pathway constitutively active and has been linked to Kaposi's sarcoma and other malignancies. In order to elucidate the molecular basis underpinning ks-vFLIP-induced activation of the IKK signalosome, we have determined the crystal structure of a complex involving a fragment of IKKγ bound to ks-vFLIP at 3.2 Å. In addition to identifying and subsequently probing the ks-vFLIP-IKKγ interface, we have also investigated the effects of a mutation implicated in the genetic disorder anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID).

Item Type: Article
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 04 Aug 2010 14:09
Last Modified: 17 Apr 2013 12:17
URI: http://eprints.bbk.ac.uk/id/eprint/1186

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