2H60

Solution Structure of Human Brg1 Bromodomain


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 11 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails

Shen, W.Xu, C.Huang, W.Zhang, J.Carlson, J.E.Tu, X.Wu, J.Shi, Y.

(2007) Biochemistry 46: 2100-2110

  • DOI: https://doi.org/10.1021/bi0611208
  • Primary Citation of Related Structures:  
    2H60

  • PubMed Abstract: 

    Human brahma-related gene 1 (Brg1) is a core protein in human SWI/SNF chromatin-remodeling complex which regulates gene expression. Brg1 contains a bromodomain that has been shown to anchor the entire complex to promoter nucleosomes by interacting with histones that are acetylated at specific lysine residues. The Brg1 bromodomain belongs to an important subclass of the bromodomain family for which no structural information is known. Here we report the solution structure of the Brg1 bromodomain determined by NMR. The Brg1 bromodomain conserves the left-handed, four-helix bundle topology found in other bromodomain structures. However, the alphaZ helix of Brg1 bromodomain is about 4 residues shorter relative to previously published bromodomain structures. Using NMR perturbation studies, we demonstrate the Brg1 bromodomain binds acetyllysine in the context of histone tails, with no comparable affinity for unacetylated peptides. The estimated dissociation constants (KD) for acetylated histone peptides H4-AcK8 and H4-AcK12 are 4.0 and 3.6 mM, respectively. In this study the dominant substrate was H3-AcK14 (KD approximately 1.2 mM). Mutagenesis analysis reveals several residues important for the binding specificity. Using molecular dynamics simulations, we present a model of the Brg1 bromodomain in complex with H3-AcK14 and discuss the potential interactions which provide the selectivity of the Brg1 bromodomain for histone H3-AcK14.


  • Organizational Affiliation

    School of Life Sciences, and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable global transcription activator SNF2L4128Homo sapiensMutation(s): 0 
EC: 3.6.1
UniProt & NIH Common Fund Data Resources
Find proteins for P51532 (Homo sapiens)
Explore P51532 
Go to UniProtKB:  P51532
PHAROS:  P51532
GTEx:  ENSG00000127616 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51532
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 11 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-13
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Data collection, Database references, Derived calculations