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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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Dimerization
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Glycosylation
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Humans
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Hydrogen Bonding
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Leucine / chemistry
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Ligands
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / metabolism
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation
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Protein Structure, Tertiary
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RNA, Double-Stranded / metabolism
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Receptors, Cell Surface / chemistry*
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Receptors, Cell Surface / metabolism
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Repetitive Sequences, Amino Acid
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Signal Transduction
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Static Electricity
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Surface Properties
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Toll-Like Receptor 3
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Toll-Like Receptors
Substances
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Ligands
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Membrane Glycoproteins
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RNA, Double-Stranded
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Receptors, Cell Surface
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TLR3 protein, human
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Toll-Like Receptor 3
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Toll-Like Receptors
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Leucine