This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2m1x

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:45, 10 September 2015

TICAM-1 TIR domain structure

Structural highlights

2m1x is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2m1w
Gene:	TICAM1, PRVTIRB, TRIF (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[TCAM1_HUMAN] Herpetic encephalitis. Herpes simplex encephalitis 4 (HSE4) [MIM: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.^[1]

Function

[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.^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sancho-Shimizu V, Perez de Diego R, Lorenzo L, Halwani R, Alangari A, Israelsson E, Fabrega S, Cardon A, Maluenda J, Tatematsu M, Mahvelati F, Herman M, Ciancanelli M, Guo Y, AlSum Z, Alkhamis N, Al-Makadma AS, Ghadiri A, Boucherit S, Plancoulaine S, Picard C, Rozenberg F, Tardieu M, Lebon P, Jouanguy E, Rezaei N, Seya T, Matsumoto M, Chaussabel D, Puel A, Zhang SY, Abel L, Al-Muhsen S, Casanova JL. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Invest. 2011 Dec;121(12):4889-902. doi: 10.1172/JCI59259. Epub 2011 Nov, 21. PMID:22105173 doi:10.1172/JCI59259
↑ Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol. 2002 Dec 15;169(12):6668-72. PMID:12471095
↑ Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol. 2003 Feb;4(2):161-7. Epub 2003 Jan 21. PMID:12539043 doi:10.1038/ni886
↑ Han KJ, Su X, Xu LG, Bin LH, Zhang J, Shu HB. Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem. 2004 Apr 9;279(15):15652-61. Epub 2004 Jan 22. PMID:14739303 doi:10.1074/jbc.M311629200
↑ Enokizono Y, Kumeta H, Funami K, Horiuchi M, Sarmiento J, Yamashita K, Standley DM, Matsumoto M, Seya T, Inagaki F. Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling. 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 doi:http://dx.doi.org/10.1073/pnas.1222811110

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m1x"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m1w|2m1w]]</td></tr>
 <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>
-<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>
+<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://pdbe.org/2m1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m1x RCSB], [http://www.ebi.ac.uk/pdbsum/2m1x PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2m1x" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2m1x

From Proteopedia

Revision as of 09:45, 10 September 2015

TICAM-1 TIR domain structure

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox