4TN3

Structure of the BBox-Coiled-coil region of Rhesus Trim5alpha


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.258 
  • R-Value Observed: 0.261 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice.

Goldstone, D.C.Walker, P.A.Calder, L.J.Coombs, P.J.Kirkpatrick, J.Ball, N.J.Hilditch, L.Yap, M.W.Rosenthal, P.B.Stoye, J.P.Taylor, I.A.

(2014) Proc Natl Acad Sci U S A 111: 9609-9614

  • DOI: https://doi.org/10.1073/pnas.1402448111
  • Primary Citation of Related Structures:  
    4TN3

  • PubMed Abstract: 

    Restriction factors (RFs) form important components of host defenses to retroviral infection. The Fv1, Trim5α, and TrimCyp RFs contain N-terminal dimerization and C-terminal specificity domains that target assembled retroviral capsid (CA) proteins enclosing the viral core. However, the molecular detail of the interaction between RFs and their CA targets is unknown. Therefore, we have determined the crystal structure of the B-box and coiled-coil (BCC) region from Trim5α and used small-angle X-ray scattering to examine the solution structure of Trim5α BCC, the dimerization domain of Fv1 (Fv1Ntd), and the hybrid restriction factor Fv1Cyp comprising Fv1NtD fused to the HIV-1 binding protein Cyclophilin A (CypA). These data reveal that coiled-coil regions of Fv1 and Trim5α form extended antiparallel dimers. In Fv1Cyp, two CypA moieties are located at opposing ends, creating a molecule with a dumbbell appearance. In Trim5α, the B-boxes are located at either end of the coiled-coil, held in place by interactions with a helical motif from the L2 region of the opposing monomer. A comparative analysis of Fv1Cyp and CypA binding to a preformed HIV-1 CA lattice reveals how RF dimerization enhances the affinity of interaction through avidity effects. We conclude that the antiparallel organization of the NtD regions of Fv1 and Trim5α dimers correctly positions C-terminal specificity and N-terminal effector domains and facilitates stable binding to adjacent CA hexamers in viral cores.


  • Organizational Affiliation

    Divisions of Molecular Structure,School of Biological Sciences, University of Auckland, Auckland, New Zealand; and d.goldstone@auckland.ac.nz itaylor@nimr.mrc.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRIM5/cyclophilin A fusion protein/T4 Lysozyme chimera
A, B
400Macaca mulattaTequatrovirus T4
This entity is chimeric
Mutation(s): 0 
Gene Names: TRIMCyp
EC: 3.2.1.17
UniProt
Find proteins for G9MAP5 (Macaca mulatta)
Explore G9MAP5 
Go to UniProtKB:  G9MAP5
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720G9MAP5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.258 
  • R-Value Observed: 0.261 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.118α = 90
b = 59.745β = 94.77
c = 146.962γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
NZ GovernmentNew ZealandRDF-UOA1102
Medical Research Council (MRC, United Kingdom)United KingdomU117565647

Revision History  (Full details and data files)

  • Version 1.0: 2014-07-16
    Type: Initial release
  • Version 1.1: 2017-09-06
    Changes: Author supporting evidence, Data collection, Database references, Derived calculations, Other, Source and taxonomy
  • Version 1.2: 2017-11-01
    Changes: Author supporting evidence
  • Version 1.3: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description