Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome. Export

@article{citeulike:2880620, 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).}, address = {Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK.}, author = {Bagn\'{e}ris, C. and Ageichik, A. V. and Cronin, N. and Wallace, B. and Collins, M. and Boshoff, C. and Waksman, G. and Barrett, T.}, citeulike-article-id = {2880620}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molcel.2008.04.029}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18538660}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18538660}, day = {6}, doi = {10.1016/j.molcel.2008.04.029}, issn = {1097-4164}, journal = {Molecular cell}, keywords = {kshv, vflip}, month = {June}, number = {5}, pages = {620--631}, posted-at = {2008-06-10 19:34:21}, priority = {0}, title = {Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome.}, url = {http://dx.doi.org/10.1016/j.molcel.2008.04.029}, volume = {30}, year = {2008} }

TY - JOUR ID - citeulike:2880620 L3 - citeulike-article-id:2880620 N2 - 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). IS - 5 JF - Molecular cell SN - 1097-4164 AD - Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK. EP - 631 TI - Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome. VL - 30 SP - 620 KW - kshv KW - vflip AU - Bagnéris, C AU - Ageichik, AV AU - Cronin, N AU - Wallace, B AU - Collins, M AU - Boshoff, C AU - Waksman, G AU - Barrett, T PY - 2008/06/06/ UR - http://dx.doi.org/10.1016/j.molcel.2008.04.029 ER -