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2z5v

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Revision as of 10:12, 20 January 2015

Solution structure of the TIR domain of human MyD88

Structural highlights

2z5v is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MYD88 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[MYD88_HUMAN] Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:612260]; also known as recurrent pyogenic bacterial infections due to MYD88 deficiency. Patients suffer from autosomal recessive, life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, and die between 1 and 11 months of age. Surviving patients are otherwise healthy, with normal resistance to other microbes, and their clinical status improved with age.^[1] ^[2]

Function

[MYD88_HUMAN] Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes (By similarity).^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal) are adaptor molecules critically involved in the Toll-like receptor (TLR) 4 signaling pathway. While Mal has been proposed to serve as a membrane-sorting adaptor, MyD88 mediates signal transduction from activated TLR4 to downstream components. The Toll/Interleukin-1 receptor (TIR) domain of MyD88 is responsible for sorting and signaling via direct or indirect TIR-TIR interactions between Mal and TLR4. However, the molecular mechanisms involved in multiple interactions of the TIR domain remain unclear. The present study describes the solution structure of the MyD88 TIR domain. Reporter gene assays revealed that 3 discrete surface sites in the TIR domain of MyD88 are important for TLR4 signaling. Two of these sites were shown to mediate direct binding to the TIR domain of Mal. Interestingly, Mal-TIR, but not MyD88-TIR, directly binds to the cytosolic TIR domain of TLR4. These observations suggested that the heteromeric assembly of TIR domains of the receptor and adaptors constitutes the initial step of TLR4 intracellular signal transduction.

Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling.,Ohnishi H, Tochio H, Kato Z, Orii KE, Li A, Kimura T, Hiroaki H, Kondo N, Shirakawa M Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10260-5. Epub 2009 Jun 8. PMID:19506249^[7]

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

References

↑ Ohnishi H, Tochio H, Kato Z, Orii KE, Li A, Kimura T, Hiroaki H, Kondo N, Shirakawa M. Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10260-5. Epub 2009 Jun 8. PMID:19506249
↑ von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, Chrabieh M, Mustapha IB, Ghandil P, Camcioglu Y, Vasconcelos J, Sirvent N, Guedes M, Vitor AB, Herrero-Mata MJ, Arostegui JI, Rodrigo C, Alsina L, Ruiz-Ortiz E, Juan M, Fortuny C, Yague J, Anton J, Pascal M, Chang HH, Janniere L, Rose Y, Garty BZ, Chapel H, Issekutz A, Marodi L, Rodriguez-Gallego C, Banchereau J, Abel L, Li X, Chaussabel D, Puel A, Casanova JL. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008 Aug 1;321(5889):691-6. PMID:18669862 doi:321/5889/691
↑ Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE. The cloning and characterization of human MyD88: a member of an IL-1 receptor related family. FEBS Lett. 1997 Jan 27;402(1):81-4. PMID:9013863
↑ Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004 Oct;5(10):1061-8. Epub 2004 Sep 7. PMID:15361868 doi:10.1038/ni1118
↑ Semaan N, Alsaleh G, Gottenberg JE, Wachsmann D, Sibilia J. Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. J Immunol. 2008 Mar 1;180(5):3485-91. PMID:18292575
↑ Ohnishi H, Tochio H, Kato Z, Orii KE, Li A, Kimura T, Hiroaki H, Kondo N, Shirakawa M. Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10260-5. Epub 2009 Jun 8. PMID:19506249
↑ Ohnishi H, Tochio H, Kato Z, Orii KE, Li A, Kimura T, Hiroaki H, Kondo N, Shirakawa M. Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10260-5. Epub 2009 Jun 8. PMID:19506249

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2z5v"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2z5v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z5V FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYD88 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYD88 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z5v RCSB], [http://www.ebi.ac.uk/pdbsum/2z5v 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=2z5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z5v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z5v RCSB], [http://www.ebi.ac.uk/pdbsum/2z5v PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/MYD88_HUMAN MYD88_HUMAN]] Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:[http://omim.org/entry/612260 612260]]; also known as recurrent pyogenic bacterial infections due to MYD88 deficiency. Patients suffer from autosomal recessive, life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, and die between 1 and 11 months of age. Surviving patients are otherwise healthy, with normal resistance to other microbes, and their clinical status improved with age.<ref>PMID:19506249</ref> <ref>PMID:18669862</ref>
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Hiroaki, H.]]
+[[Category: Hiroaki, H]]
-[[Category: Kato, Z.]]
+[[Category: Kato, Z]]
-[[Category: Kondo, N.]]
+[[Category: Kondo, N]]
-[[Category: Ohnishi, H.]]
+[[Category: Ohnishi, H]]
-[[Category: Shirakawa, M.]]
+[[Category: Shirakawa, M]]
-[[Category: Tochio, H.]]
+[[Category: Tochio, H]]
 [[Category: Immune response]]
 [[Category: Immune system]]
 [[Category: Inflammatory response]]
 [[Category: Signal transduction innate immunity]]

2z5v

From Proteopedia

Revision as of 10:12, 20 January 2015

Solution structure of the TIR domain of human MyD88

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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