View source for 2m1w


==TICAM-2 TIR domain==
<StructureSection load='2m1w' size='340' side='right'caption='[[2m1w]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2m1w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M1W FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m1w OCA], [https://pdbe.org/2m1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m1w RCSB], [https://www.ebi.ac.uk/pdbsum/2m1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m1w ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TCAM2_HUMAN TCAM2_HUMAN] Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.<ref>PMID:12721283</ref> <ref>PMID:14519765</ref> <ref>PMID:14517278</ref> <ref>PMID:194121844</ref> <ref>PMID:16603631</ref> <ref>PMID:16757566</ref> <ref>PMID:22685567</ref>   Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.<ref>PMID:12721283</ref> <ref>PMID:14519765</ref> <ref>PMID:14517278</ref> <ref>PMID:194121844</ref> <ref>PMID:16603631</ref> <ref>PMID:16757566</ref> <ref>PMID:22685567</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2m1w" style="background-color:#fffaf0;"></div>

==See Also==
*[[TIR domain-containing adapter protein|TIR domain-containing adapter protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Enokizono Y]]
[[Category: Funami K]]
[[Category: Horiuchi M]]
[[Category: Inagaki F]]
[[Category: Kumeta H]]
[[Category: Matsumoto M]]
[[Category: Sarmiento J]]
[[Category: Seya T]]
[[Category: Standley DM]]
[[Category: Yamashita K]]