3CL3

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

Summary for 3CL3

• Entry DOI: 10.2210/pdb3cl3/pdb
• Descriptor: ORF K13, NF-kappa-B essential modulator (2 entities in total)
• Functional Keywords: death effector domain, coiled-coil, coiled coil, cytoplasm, disease mutation, ectodermal dysplasia, host-virus interaction, nucleus, transcription, transcription regulation, viral protein-signaling protein complex, viral protein/signaling protein
• Biological source: Human gammaherpesvirus 8; More
• Total number of polymer chains: 4
• Total formula weight: 70846.87

Authors

Bagneris, C.,Ageichik, A.V.,Cronin, N.,Boshoff, C.,Waksman, G.,Barrett, T. (deposition date: 2008-03-18, release date: 2008-06-17, Last modification date: 2024-02-21)

Primary citation

Bagneris, C.,Ageichik, A.V.,Cronin, N.,Wallace, B.,Collins, M.,Boshoff, C.,Waksman, G.,Barrett, T.
Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome.
Mol.Cell, 30:620-631, 2008

PubMed Abstract: 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).

PubMed: 18538660
DOI: 10.1016/j.molcel.2008.04.029

Experimental method

X-RAY DIFFRACTION (3.2 Å)