3cl3

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Template:STRUCTURE 3cl3

Crystal Structure of a vFLIP-IKKgamma complex: Insights into viral activation of the IKK signalosome

Overview

Key to the pathogenicity of several viruses is activation of the canonical nuclear factor-kappaB (NF-kappaB) 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 IKKgamma, an essential component of the IKK complex or signalosome. This interaction renders the canonical NF-kappaB 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 IKKgamma bound to ks-vFLIP at 3.2 A. In addition to identifying and subsequently probing the ks-vFLIP-IKKgamma interface, we have also investigated the effects of a mutation implicated in the genetic disorder anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID).

About this Structure

3CL3 is a Protein complex structure of sequences from Homo sapiens and Human herpesvirus 8. Full crystallographic information is available from OCA.

Reference

Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome., Bagneris C, Ageichik AV, Cronin N, Wallace B, Collins M, Boshoff C, Waksman G, Barrett T, Mol Cell. 2008 Jun 6;30(5):620-31. PMID:18538660 Page seeded by OCA on Wed Jun 18 12:10:46 2008