6R80

Structure of AFF4 C-terminal homology domain

  • Classification: TRANSCRIPTION
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli
  • Mutation(s): No 

  • Deposited: 2019-03-30 Released: 2019-06-12 
  • Deposition Author(s): Chen, Y., Cramer, P.
  • Funding Organization(s): German Research Foundation, European Research Council, Volkswagen Foundation

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization.

Chen, Y.Cramer, P.

(2019) J Biol Chem 294: 10663-10673

  • DOI: https://doi.org/10.1074/jbc.RA119.008577
  • Primary Citation of Related Structures:  
    6R80

  • PubMed Abstract: 

    AF4/FMR2 family member 4 (AFF4) is the scaffold protein of the multisubunit super-elongation complex, which plays key roles in the release of RNA polymerase II from promoter-proximal pausing and in the transactivation of HIV-1 transcription. AFF4 consists of an intrinsically disordered N-terminal region that interacts with other super-elongation complex subunits and a C-terminal homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. Here, we solved the X-ray crystal structure of the CHD in human AFF4 (AFF4-CHD) to 2.2 Å resolution and characterized its biochemical properties. The structure disclosed that AFF4-CHD folds into a novel domain that consists of eight helices and is distantly related to tetratrico peptide repeat motifs. Our analyses further revealed that AFF4-CHD mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. Results from fluorescence anisotropy experiments suggested that AFF4-CHD interacts with both RNA and DNA in vitro Furthermore, we identified a surface loop region in AFF4-CHD as a substrate for the P-TEFb kinase cyclin-dependent kinase 9, which triggers release of polymerase II from promoter-proximal pausing sites. In conclusion, the AFF-CHD structure and biochemical analyses reported here reveal the molecular basis for the homo- and heterodimerization of AFF proteins and implicate the AFF4-CHD in nucleic acid interactions. The high conservation of the CHD among several other proteins suggests that our results are also relevant for understanding other CHD-containing proteins and their dimerization behavior.


  • Organizational Affiliation

    From the Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AF4/FMR2 family member 4284Homo sapiensMutation(s): 0 
Gene Names: AFF4AF5Q31MCEFHSPC092
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UHB7 (Homo sapiens)
Explore Q9UHB7 
Go to UniProtKB:  Q9UHB7
PHAROS:  Q9UHB7
GTEx:  ENSG00000072364 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UHB7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.233 
  • Space Group: I 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.53α = 90
b = 79.48β = 90
c = 185.44γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
HKL2Mapphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanySFB860
German Research FoundationGermanySPP1935
European Research CouncilGermanyTRANSREGULON, No 693023
Volkswagen FoundationGermany--

Revision History  (Full details and data files)

  • Version 1.0: 2019-06-12
    Type: Initial release
  • Version 1.1: 2019-07-17
    Changes: Data collection, Database references