3ULS

Crystal structure of Fab12


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Lateral Clustering of TLR3:dsRNA Signaling Units Revealed by TLR3ecd:3Fabs Quaternary Structure.

Luo, J.Obmolova, G.Malia, T.J.Wu, S.J.Duffy, K.E.Marion, J.D.Bell, J.K.Ge, P.Zhou, Z.H.Teplyakov, A.Zhao, Y.Lamb, R.J.Jordan, J.L.San Mateo, L.R.Sweet, R.W.Gilliland, G.L.

(2012) J Mol Biol 421: 112-124

  • DOI: https://doi.org/10.1016/j.jmb.2012.05.006
  • Primary Citation of Related Structures:  
    3ULS, 3ULU, 3ULV

  • PubMed Abstract: 

    Toll-like receptor 3 (TLR3) recognizes dsRNA and initiates an innate immune response through the formation of a signaling unit (SU) composed of one double-stranded RNA (dsRNA) and two TLR3 molecules. We report the crystal structure of human TLR3 ectodomain (TLR3ecd) in a quaternary complex with three neutralizing Fab fragments. Fab15 binds an epitope that overlaps the C-terminal dsRNA binding site and, in biochemical assays, blocks the interaction of TLR3ecd with dsRNA, thus directly antagonizing TLR3 signaling through inhibition of SU formation. In contrast, Fab12 and Fab1068 bind TLR3ecd at sites distinct from the N- and C-terminal regions that interact with dsRNA and do not inhibit minimal SU formation with short dsRNA. Molecular modeling based on the co-structure rationalizes these observations by showing that both Fab12 and Fab1068 prevent lateral clustering of SUs along the length of the dsRNA ligand. This model is further supported by cell-based assay results using dsRNA ligands of lengths that support single and multiple SUs. Thus, their antagonism of TLR3 signaling indicates that lateral clustering of SUs is required for TLR3 signal transduction.


  • Organizational Affiliation

    Biologics Research, Janssen Research and Development, L.L.C., 145 King of Prussia Road, Radnor, PA 19087, USA. jluo@its.jnj.com


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fab12 light chainA [auth L],
C [auth A]
213Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab12 heavy chainB [auth H],
D [auth B]
226Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
A [auth L],
C [auth A]
L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.8α = 90
b = 80.21β = 115.6
c = 83.05γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
XDSdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-23
    Type: Initial release
  • Version 1.1: 2012-05-30
    Changes: Database references
  • Version 1.2: 2012-07-25
    Changes: Database references
  • Version 2.0: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Polymer sequence, Refinement description