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). © 2008 Elsevier Inc. All rights reserved.
Bagnéris, C., Ageichik, A. V., Cronin, N., Wallace, B., Collins, M., Boshoff, C., … Barrett, T. (2008). Crystal Structure of a vFlip-IKKγ Complex: Insights into Viral Activation of the IKK Signalosome. Molecular Cell, 30(5), 620–631. https://doi.org/10.1016/j.molcel.2008.04.029