2k2u
From Proteopedia
NMR Structure of the complex between Tfb1 subunit of TFIIH and the activation domain of VP16
Structural highlights
Function[TFB1_YEAST] Acts as component of the general transcription and DNA repair factor IIH (TFIIH) core, which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activity, and is essential for polymerase II transcription in vitro.[1] [2] [VP16_HHV1F] Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional regulatory VP16-induced complex composed of VP16 and two cellular factors, HCFC1 and POU2F 1. VP16-induced complex represents a regulatory switch: when it is on, it promotes IE-gene expression and thus lytic infection, and when it is off, it limits IE-gene transcription favoring latent infection (By similarity). May play a role in the aggregation of tegument proteins around nucleocapsids during virus morphogenesis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Herpes Simplex Virion Protein 16 (VP16) activates transcription through a series of protein/protein interactions involving its highly acidic transactivation domain (TAD). The acidic TAD of VP16 (VP16TAD) has been shown to interact with several partner proteins both in vitro and in vivo, and many of these VP16 partners also bind the acidic TAD of the mammalian tumor suppressor protein p53. For example, the TADs of VP16 and p53 (p53TAD) both interact directly with the p62/Tfb1 (human/yeast) subunit of TFIIH, and this interaction correlates with their ability to activate both the initiation and elongation phase of transcription. In this manuscript, we use NMR spectroscopy, isothermal titration calorimetery (ITC) and site-directed mutagenesis studies to characterize the interaction between the VP16TAD and Tfb1. We identify a region within the carboxyl-terminal subdomain of the VP16TAD (VP16C) that has sequence similarity with p53TAD2 and binds Tfb1 with nanomolar affinity. We determine an NMR structure of a Tfb1/VP16C complex, which represents the first high-resolution structure of the VP16TAD in complex with a target protein. The structure demonstrates that like p53TAD2, VP16C forms a 9-residue alpha-helix in complex with Tfb1. Comparison of the VP16/Tfb1and p53/Tfb1 structures clearly demonstrates how the viral activator VP16C and p53TAD2 shares numerous aspects of binding to Tfb1. Despite the similarities, important differences are observed between the p53TAD2/Tfb1 and VP16C/Tfb1 complexes, and these differences demonstrate how selected activators such as p53 depend on phosphorylation events to selectively regulate transcription. NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: structural similarities between VP16 and p53.,Langlois C, Mas C, Di Lello P, Jenkins LM, Legault P, Omichinski JG J Am Chem Soc. 2008 Aug 13;130(32):10596-604. Epub 2008 Jul 17. PMID:18630911[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human herpesvirus 1 | Large Structures | Saccharomyces cerevisiae | Jenkins, P M.Miller | Langlois, C | Legault, J | Lello, P Di | Mas, C | Omichinski, J G | Activation | Dna damage | Dna repair | Dna-binding | Nucleus | Ph domain | Protein structure complex | Tfb1 | Tfiih | Transcription | Transcription regulation | Vp16
