1fyw
From Proteopedia
(New page: 200px<br /> <applet load="1fyw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fyw, resolution 3.0Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1fyw.gif|left|200px]]<br /> | + | [[Image:1fyw.gif|left|200px]]<br /><applet load="1fyw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fyw" size=" | + | |
caption="1fyw, resolution 3.0Å" /> | caption="1fyw, resolution 3.0Å" /> | ||
'''CRYSTAL STRUCTURE OF THE TIR DOMAIN OF HUMAN TLR2'''<br /> | '''CRYSTAL STRUCTURE OF THE TIR DOMAIN OF HUMAN TLR2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Toll-like receptors (TLRs) and the interleukin-1 receptor superfamily | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FYW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1FYW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Horng, T.]] | [[Category: Horng, T.]] | ||
| - | [[Category: Manley, J | + | [[Category: Manley, J L.]] |
[[Category: Medzhitov, R.]] | [[Category: Medzhitov, R.]] | ||
| - | [[Category: NESG, Northeast | + | [[Category: NESG, Northeast Structural Genomics Consortium.]] |
[[Category: Shen, B.]] | [[Category: Shen, B.]] | ||
[[Category: Tao, X.]] | [[Category: Tao, X.]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:05 2008'' |
Revision as of 10:44, 21 February 2008
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CRYSTAL STRUCTURE OF THE TIR DOMAIN OF HUMAN TLR2
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Colorectal cancer, susceptibility to OMIM:[603028], Leprosy, susceptibility to OMIM:[603028]
About this Structure
1FYW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for signal transduction by the Toll/interleukin-1 receptor domains., Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L, Nature. 2000 Nov 2;408(6808):111-5. PMID:11081518
Page seeded by OCA on Thu Feb 21 12:44:05 2008
Categories: Homo sapiens | Single protein | Horng, T. | Manley, J L. | Medzhitov, R. | NESG, Northeast Structural Genomics Consortium. | Shen, B. | Tao, X. | Tong, L. | Xu, Y. | Beta-alpha-beta fold parallel beta sheet | Nesg | Northeast structural genomics consortium | Protein structure initiative | Psi | Structural genomics
