Abstract
Toll-like receptors (TLRs) are important pattern recognition receptors that function in innate immunity. Elucidating the structure and signaling mechanisms of TLR9, a sensor of foreign and endogenous DNA, is essential for understanding its key role in immunity against microbial pathogens as well as in autoimmunity. Abundant evidence suggests that the TLR9-CTD (C-terminal domain) by itself is capable of DNA binding and signaling. The crystal structure of unliganded mouse TLR9-CTD is presented. TLR9-CTD exhibits one unique feature, a cluster of stacked aromatic and arginine side chains on its concave face. Overall, its structure is most related to the TLR8-CTD, suggesting a similar mode of ligand binding and signaling.
Keywords:
DNA; LRR; TLR; TLR9; Toll-like receptor; innate immunity; leucine-rich repeat; nucleic acid.
© 2014 Wiley Periodicals, Inc.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Crystallography, X-Ray
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Databases, Protein
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Humans
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Mice
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Models, Molecular*
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Peptide Fragments / chemistry*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Conformation
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Protein Interaction Domains and Motifs
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Toll-Like Receptor 3 / chemistry
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / metabolism
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Toll-Like Receptor 8 / chemistry
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Toll-Like Receptor 8 / genetics
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Toll-Like Receptor 8 / metabolism
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Toll-Like Receptor 9 / chemistry*
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / metabolism
Substances
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Peptide Fragments
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Recombinant Fusion Proteins
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Recombinant Proteins
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TLR3 protein, human
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TLR8 protein, human
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Tlr9 protein, mouse
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Toll-Like Receptor 3
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Toll-Like Receptor 8
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Toll-Like Receptor 9