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2mk9

From Proteopedia

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Current revision

Spatial structure of the dimeric transmembrane domain of Toll-like receptor 3

Structural highlights

2mk9 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TLR3_HUMAN Defects in TLR3 are associated with herpes simplex encephalitis type 2 (HSE2) [MIM:613002. HSE is 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=TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.^[1]

Function

TLR3_HUMAN Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Toll-like receptors (TLRs) take part in both the innate and adaptive immune systems. The role of the transmembrane domain in TLR signaling is still elusive, while its importance for the TLR activation was clearly demonstrated. In the present study the ability of the TLR3 transmembrane domain to form dimers and trimers in detergent micelles was shown by solution NMR spectroscopy. Spatial structures and free energy magnitudes were determined for the TLR3 transmembrane domain in dimeric and trimeric states, and two possible surfaces that may be used for the helix-helix interaction by the full-length TLR3 were revealed.

Toll-like receptor 3 transmembrane domain is able to perform various homotypic interactions: An NMR structural study.,Mineev KS, Goncharuk SA, Arseniev AS FEBS Lett. 2014 Sep 12. pii: S0014-5793(14)00658-9. doi:, 10.1016/j.febslet.2014.08.031. PMID:25217833^[8]

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

References

↑ Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007 Sep 14;317(5844):1522-7. PMID:17872438 doi:317/5844/1522
↑ de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C. Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem. 2005 Nov 18;280(46):38133-45. Epub 2005 Sep 6. PMID:16144834 doi:M507163200
↑ Johnsen IB, Nguyen TT, Ringdal M, Tryggestad AM, Bakke O, Lien E, Espevik T, Anthonsen MW. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. EMBO J. 2006 Jul 26;25(14):3335-46. Epub 2006 Jul 6. PMID:16858407 doi:7601222
↑ Bell JK, Askins J, Hall PR, Davies DR, Segal DM. The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8792-7. Epub 2006 May 23. PMID:16720699 doi:10.1073/pnas.0603245103
↑ Sarkar SN, Elco CP, Peters KL, Chattopadhyay S, Sen GC. Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation. J Biol Chem. 2007 Feb 9;282(6):3423-7. Epub 2006 Dec 18. PMID:17178723 doi:C600226200
↑ Leonard JN, Ghirlando R, Askins J, Bell JK, Margulies DH, Davies DR, Segal DM. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):258-63. doi: 10.1073/pnas.0710779105., Epub 2008 Jan 2. PMID:18172197 doi:10.1073/pnas.0710779105
↑ Bell JK, Botos I, Hall PR, Askins J, Shiloach J, Segal DM, Davies DR. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10976-80. Epub 2005 Jul 25. PMID:16043704
↑ Mineev KS, Goncharuk SA, Arseniev AS. Toll-like receptor 3 transmembrane domain is able to perform various homotypic interactions: An NMR structural study. FEBS Lett. 2014 Sep 12. pii: S0014-5793(14)00658-9. doi:, 10.1016/j.febslet.2014.08.031. PMID:25217833 doi:http://dx.doi.org/10.1016/j.febslet.2014.08.031

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mk9"

Categories: Homo sapiens | Large Structures | Arseniev AS | Goncharuk SA | Mineev KS

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2mk9]] is a 2 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=2MK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MK9 FirstGlance]. <br>
-</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=2mk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mk9 OCA], [https://pdbe.org/2mk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mk9 RCSB], [https://www.ebi.ac.uk/pdbsum/2mk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mk9 ProSAT]</span></td></tr>
+</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=2mk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mk9 OCA], [https://pdbe.org/2mk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mk9 RCSB], [https://www.ebi.ac.uk/pdbsum/2mk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mk9 ProSAT]</span></td></tr>
 </table>
 == Disease ==

2mk9

From Proteopedia

Current revision

Spatial structure of the dimeric transmembrane domain of Toll-like receptor 3

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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