2K2U

NMR Structure of the complex between Tfb1 subunit of TFIIH and the activation domain of VP16


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

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, L.M.Legault, P.Omichinski, J.G.

(2008) J Am Chem Soc 130: 10596-10604

  • DOI: https://doi.org/10.1021/ja800975h
  • Primary Citation of Related Structures:  
    2K2U

  • PubMed Abstract: 

    The 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.


  • Organizational Affiliation

    Département de Biochimie, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7 Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA polymerase II transcription factor B subunit 1115Saccharomyces cerevisiaeMutation(s): 1 
Gene Names: TFB1YDR311WD9740.3
UniProt
Find proteins for P32776 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P32776 
Go to UniProtKB:  P32776
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP32776
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha trans-inducing protein35N/AMutation(s): 0 
Gene Names: UL48
UniProt
Find proteins for P04486 (Human herpesvirus 1 (strain F))
Explore P04486 
Go to UniProtKB:  P04486
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04486
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations