2m1x

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{{STRUCTURE_2m1x| PDB=2m1x | SCENE= }}
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==TICAM-1 TIR domain structure==
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===TICAM-1 TIR domain structure===
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<StructureSection load='2m1x' size='340' side='right' caption='[[2m1x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_24255114}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2m1x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M1X FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m1w|2m1w]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TICAM1, PRVTIRB, TRIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2m1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m1x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m1x RCSB], [http://www.ebi.ac.uk/pdbsum/2m1x PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/TCAM1_HUMAN TCAM1_HUMAN]] Herpetic encephalitis. Herpes simplex encephalitis 4 (HSE4) [MIM:[http://omim.org/entry/614850 614850]]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:22105173</ref>
[[http://www.uniprot.org/uniprot/TCAM1_HUMAN TCAM1_HUMAN]] Herpetic encephalitis. Herpes simplex encephalitis 4 (HSE4) [MIM:[http://omim.org/entry/614850 614850]]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:22105173</ref>
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== Function ==
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==Function==
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[[http://www.uniprot.org/uniprot/TCAM1_HUMAN TCAM1_HUMAN]] Involved in innate immunity against invading pathogens. Adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively.<ref>PMID:12471095</ref> <ref>PMID:12539043</ref> <ref>PMID:14739303</ref>
[[http://www.uniprot.org/uniprot/TCAM1_HUMAN TCAM1_HUMAN]] Involved in innate immunity against invading pathogens. Adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively.<ref>PMID:12471095</ref> <ref>PMID:12539043</ref> <ref>PMID:14739303</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Homotypic and heterotypic interactions between Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors (TLRs) and downstream adaptors are essential to evoke innate immune responses. However, such oligomerization properties present intrinsic difficulties in structural studies of TIR domains. Here, using BB-loop mutations that disrupt homotypic interactions, we determined the structures of the monomeric TIR domain-containing adaptor molecule (TICAM)-1 and TICAM-2 TIR domains. Docking of the monomeric structures, together with yeast two hybrid-based mutagenesis assays, reveals that the homotypic interaction between TICAM-2 TIR is indispensable to present a scaffold for recruiting the monomeric moiety of the TICAM-1 TIR dimer. This result proposes a unique idea that oligomerization of upstream TIR domains is crucial for binding of downstream TIR domains. Furthermore, the bivalent nature of each TIR domain dimer can generate a large signaling complex under the activated TLRs, which would recruit downstream signaling molecules efficiently. This model is consistent with previous reports that BB-loop mutants completely abrogate downstream signaling.
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==About this Structure==
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Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling.,Enokizono Y, Kumeta H, Funami K, Horiuchi M, Sarmiento J, Yamashita K, Standley DM, Matsumoto M, Seya T, Inagaki F Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19908-13. doi:, 10.1073/pnas.1222811110. Epub 2013 Nov 19. PMID:24255114<ref>PMID:24255114</ref>
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[[2m1x]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M1X OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024255114</ref><references group="xtra"/><references/>
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</div>
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[[Category: Enokizono, Y.]]
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== References ==
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[[Category: Funami, K.]]
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<references/>
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[[Category: Horiuchi, M.]]
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__TOC__
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[[Category: Inagaki, F.]]
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</StructureSection>
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[[Category: Kumeta, H.]]
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[[Category: Human]]
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[[Category: Matsumoto, M.]]
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[[Category: Enokizono, Y]]
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[[Category: Sarmiento, J.]]
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[[Category: Funami, K]]
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[[Category: Seya, T.]]
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[[Category: Horiuchi, M]]
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[[Category: Standley, D M.]]
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[[Category: Inagaki, F]]
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[[Category: Yamashita, K.]]
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[[Category: Kumeta, H]]
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[[Category: Matsumoto, M]]
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[[Category: Sarmiento, J]]
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[[Category: Seya, T]]
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[[Category: Standley, D M]]
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[[Category: Yamashita, K]]
[[Category: Immune system]]
[[Category: Immune system]]
[[Category: Innate immunity]]
[[Category: Innate immunity]]

Revision as of 06:48, 22 December 2014

TICAM-1 TIR domain structure

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