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PDBsum entry 3cig
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Immune system
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PDB id
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3cig
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References listed in PDB file
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Key reference
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Title
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Structural basis of toll-Like receptor 3 signaling with double-Stranded RNA.
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Authors
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L.Liu,
I.Botos,
Y.Wang,
J.N.Leonard,
J.Shiloach,
D.M.Segal,
D.R.Davies.
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Ref.
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Science, 2008,
320,
379-381.
[DOI no: ]
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PubMed id
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Abstract
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Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular
signature of most viruses, and triggers inflammatory responses that prevent
viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least
40 to 50 base pairs in length, the minimal length required for signal
transduction. To establish the molecular basis for ligand binding and signaling,
we determined the crystal structure of a complex between two mouse TLR3-ECDs and
dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located
at opposite ends of the TLR3 horseshoe, and an intermolecular contact between
the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This
juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic
Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD
does not change upon binding to dsRNA.
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Figure 1.
Fig. 1. dsRNA:TLR3 signaling complex. Mouse TLR3 ectodomains
(green and cyan) form a dimer on the dsRNA (blue and red). The N
glycans are shown (light green and light blue). (A) The N-and
C-terminal binding sites. (B) Illustration of how the two
C-terminal domains are brought together in the complex. Figures
generated with PyMol (DeLano Scientific, San Carlos, CA).
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Figure 3.
Fig. 3. Closeup of the C-terminal domain interacting residues.
Some of these residues (678 to 681) are located on a conserved
loop observed in other TLR structures.
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The above figures are
reprinted
from an Open Access publication published by the AAAs:
Science
(2008,
320,
379-381)
copyright 2008.
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