4D5T

Structure of N-terminally truncated A49 from Vaccinia Virus Western Reserve


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Vaccinia Virus Protein A49 is an Unexpected Member of the B-Cell Lymphoma (Bcl)-2 Protein Family

Neidel, S.Maluquer De Motes, C.Mansur, D.S.Strnadova, P.Smith, G.L.Graham, S.C.

(2015) J Biol Chem 290: 5991

  • DOI: https://doi.org/10.1074/jbc.M114.624650
  • Primary Citation of Related Structures:  
    4D5R, 4D5S, 4D5T

  • PubMed Abstract: 

    Vaccinia virus (VACV) encodes several proteins that inhibit activation of the proinflammatory transcription factor nuclear factor κB (NF-κB). VACV protein A49 prevents translocation of NF-κB to the nucleus by sequestering cellular β-TrCP, a protein required for the degradation of the inhibitor of κB. A49 does not share overall sequence similarity with any protein of known structure or function. We solved the crystal structure of A49 from VACV Western Reserve to 1.8 Å resolution and showed, surprisingly, that A49 has the same three-dimensional fold as Bcl-2 family proteins despite lacking identifiable sequence similarity. Whereas Bcl-2 family members characteristically modulate cellular apoptosis, A49 lacks a surface groove suitable for binding BH3 peptides and does not bind proapoptotic Bcl-2 family proteins Bax or Bak. The N-terminal 17 residues of A49 do not adopt a single well ordered conformation, consistent with their proposed role in binding β-TrCP. Whereas pairs of A49 molecules interact symmetrically via a large hydrophobic surface in crystallo, A49 does not dimerize in solution or in cells, and we propose that this hydrophobic interaction surface may mediate binding to a yet undefined cellular partner. A49 represents the eleventh VACV Bcl-2 family protein and, despite these proteins sharing very low sequence identity, structure-based phylogenetic analysis shows that all poxvirus Bcl-2 proteins are structurally more similar to each other than they are to any cellular or herpesvirus Bcl-2 proteins. This is consistent with duplication and diversification of a single BCL2 family gene acquired by an ancestral poxvirus.


  • Organizational Affiliation

    From the Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN A49R
A, B, C, D, E
A, B, C, D, E, F, G, H
160Vaccinia virus Western ReserveMutation(s): 0 
UniProt
Find proteins for P31037 (Vaccinia virus (strain Western Reserve))
Explore P31037 
Go to UniProtKB:  P31037
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31037
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.29α = 90
b = 45.63β = 98.74
c = 160.26γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-21
    Type: Initial release
  • Version 1.1: 2015-01-28
    Changes: Database references
  • Version 1.2: 2015-08-12
    Changes: Database references
  • Version 1.3: 2019-05-08
    Changes: Data collection, Experimental preparation, Other
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description