Crystal structure of human toll-like receptor 3 (TLR3) ectodomain

Science. 2005 Jul 22;309(5734):581-5. doi: 10.1126/science.1115253. Epub 2005 Jun 16.

Abstract

Toll-like receptors (TLRs) play key roles in activating immune responses during infection. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Asparagines conserved in the 24-residue LRR motif contribute extensive hydrogen-bonding networks for solenoid stabilization. TLR3 is largely masked by carbohydrate, but one face is glycosylation-free, which suggests its potential role in ligand binding and oligomerization. Highly conserved surface residues and a TLR3-specific LRR insertion form a homodimer interface in the crystal, whereas two patches of positively charged residues and a second insertion would provide an appropriate binding site for double-stranded RNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Glycosylation
  • Humans
  • Hydrogen Bonding
  • Leucine / chemistry
  • Ligands
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / metabolism
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism
  • Repetitive Sequences, Amino Acid
  • Signal Transduction
  • Static Electricity
  • Surface Properties
  • Toll-Like Receptor 3
  • Toll-Like Receptors

Substances

  • Ligands
  • Membrane Glycoproteins
  • RNA, Double-Stranded
  • Receptors, Cell Surface
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Leucine

Associated data

  • PDB/1ZIW