1FYV

CRYSTAL STRUCTURE OF THE TIR DOMAIN OF HUMAN TLR1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.254 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for signal transduction by the Toll/interleukin-1 receptor domains.

Xu, Y.Tao, X.Shen, B.Horng, T.Medzhitov, R.Manley, J.L.Tong, L.

(2000) Nature 408: 111-115

  • DOI: https://doi.org/10.1038/35040600
  • Primary Citation of Related Structures:  
    1FYV, 1FYW, 1FYX

  • PubMed Abstract: 

    Toll-like receptors (TLRs) and the interleukin-1 receptor superfamily (IL-1Rs) are integral to both innate and adaptive immunity for host defence. These receptors share a conserved cytoplasmic domain, known as the TIR domain. A single-point mutation in the TIR domain of murine TLR4 (Pro712His, the Lps(d) mutation) abolishes the host immune response to lipopolysaccharide (LPS), and mutation of the equivalent residue in TLR2, Pro681His, disrupts signal transduction in response to stimulation by yeast and gram-positive bacteria. Here we report the crystal structures of the TIR domains of human TLR1 and TLR2 and of the Pro681His mutant of TLR2. The structures have a large conserved surface patch that also contains the site of the Lps(d) mutation. Mutagenesis and functional studies confirm that residues in this surface patch are crucial for receptor signalling. The Lps(d) mutation does not disturb the structure of the TIR domain itself. Instead, structural and functional studies indicate that the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule, and that the Lps(d) mutation may abolish receptor signalling by disrupting this recruitment.


  • Organizational Affiliation

    Department of Biological Sciences, Columbia University, New York, New York 10027, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TOLL-LIKE RECEPTOR 1161Homo sapiensMutation(s): 2 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15399 (Homo sapiens)
Explore Q15399 
Go to UniProtKB:  Q15399
PHAROS:  Q15399
GTEx:  ENSG00000174125 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15399
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: 2.90 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.254 
  • Space Group: P 64 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.3α = 90
b = 101.3β = 90
c = 137.9γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MADSYSphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-11-22
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Advisory, Experimental preparation