4eo7 - Revision history

OCA at 10:48, 6 November 2024

2024-11-06T10:48:56Z

← Older revision		Revision as of 10:48, 6 November 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>		[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.

			Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.,Snyder GA, Cirl C, Jiang J, Chen K, Waldhuber A, Smith P, Rommler F, Snyder N, Fresquez T, Durr S, Tjandra N, Miethke T, Xiao TS Proc Natl Acad Sci U S A. 2013 Apr 8. PMID:23569230<ref>PMID:23569230</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4eo7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 15:06, 14 March 2024

2024-03-14T15:06:05Z

← Older revision		Revision as of 15:06, 14 March 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>		[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.

	Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.,Snyder GA, Cirl C, Jiang J, Chen K, Waldhuber A, Smith P, Rommler F, Snyder N, Fresquez T, Durr S, Tjandra N, Miethke T, Xiao TS Proc Natl Acad Sci U S A. 2013 Apr 8. PMID:23569230<ref>PMID:23569230</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4eo7" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 08:21, 6 December 2023

2023-12-06T08:21:47Z

← Older revision		Revision as of 08:21, 6 December 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eo7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EO7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eo7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EO7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.449Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo7 OCA], [https://pdbe.org/4eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/4eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo7 ProSAT]</span></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=4eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo7 OCA], [https://pdbe.org/4eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/4eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/MYD88_HUMAN MYD88_HUMAN]] Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:[https://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>		[https://www.uniprot.org/uniprot/MYD88_HUMAN MYD88_HUMAN] Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:[https://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>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>		[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:20, 28 September 2022

2022-09-28T07:20:29Z

← Older revision		Revision as of 07:20, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.==		==Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.==
	<StructureSection load='4eo7' size='340' side='right' caption='[[4eo7]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='4eo7' size='340' side='right'caption='[[4eo7]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eo7]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EO7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eo7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EO7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	~~<tr~~ id~~='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class~~="~~sblockDat~~"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene><~~/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=4eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo7 OCA], [https://pdbe.org/4eo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eo7 RCSB], [https://www.ebi.ac.uk/pdbsum/4eo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo7 ProSAT]</span></td></tr>
	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat">[[4dom\|4dom]]</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 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=4eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo7 OCA], [~~http~~://pdbe.org/4eo7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eo7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eo7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>		[[https://www.uniprot.org/uniprot/MYD88_HUMAN MYD88_HUMAN]] Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:[https://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>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>		[[https://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4eo7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eo7" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[TIR domain-containing adapter protein\|TIR domain-containing adapter protein]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Chen, P]]		[[Category: Large Structures]]
	[[Category: Cirl, C]]		[[Category: Chen P]]
	[[Category: Jiang~~, J S~~]]		[[Category: Cirl C]]
	[[Category: Smith, T]]		[[Category: Jiang JS]]
	[[Category: Snyder~~, G A~~]]		[[Category: Smith T]]
	[[Category: Xiao~~, T S]]~~		[[Category: Snyder GA]]
	~~[[Category: Adapter protein]]~~		[[Category: Xiao TS]]
	~~[[Category: Beta-alpha-beta fold]]~~
	~~[[Category: Innate immune signaling]]~~
	~~[[Category: Parallel beta sheet]]~~
	~~[[Category: Protein binding]]~~
	~~[[Category: Signaling protein]]~~
	~~[[Category: Tir-domain]]~~
	~~[[Category: Tirap/mal]]~~
	~~[[Category: Toll like receptor~~]]

OCA at 13:49, 4 August 2016

2016-08-04T13:49:25Z

← Older revision		Revision as of 13:49, 4 August 2016
Line 1:		Line 1:
	~~{{STRUCTURE_4eo7\| PDB=4eo7 \| SCENE= }}~~
	~~===Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.===~~
	~~{{ABSTRACT_PUBMED_23569230}}~~

	==Disease==		==Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.==
			<StructureSection load='4eo7' size='340' side='right' caption='[[4eo7]], [[Resolution\|resolution]] 1.45Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4eo7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EO7 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dom\|4dom]]</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 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=4eo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eo7 OCA], [http://pdbe.org/4eo7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eo7 RCSB], [http://www.ebi.ac.uk/pdbsum/4eo7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eo7 ProSAT]</span></td></tr>
			</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>		[[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>
			== Function ==
	==Function==
	[[http://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>		[[http://www.uniprot.org/uniprot/MYD88_HUMAN 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).<ref>PMID:9013863</ref> <ref>PMID:15361868</ref> <ref>PMID:18292575</ref> <ref>PMID:19506249</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.

	~~==About this Structure==~~		Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.,Snyder GA, Cirl C, Jiang J, Chen K, Waldhuber A, Smith P, Rommler F, Snyder N, Fresquez T, Durr S, Tjandra N, Miethke T, Xiao TS Proc Natl Acad Sci U S A. 2013 Apr 8. PMID:23569230<ref>PMID:23569230</ref>
	~~[[4eo7]] is a 1 chain structure with sequence~~ from ~~[http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4EO7 OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	<references ~~group="xtra"~~/><~~references~~/>		</div>
	[[Category: ~~Homo sapiens~~]]		<div class="pdbe-citations 4eo7" style="background-color:#fffaf0;"></div>
	[[Category: Chen, P.]]		== References ==
	[[Category: Cirl, C.]]		<references/>
	[[Category: Jiang, J S.]]		__TOC__
	[[Category: Smith, T.]]		</StructureSection>
	[[Category: Snyder, G A.]]		[[Category: Human]]
	[[Category: Xiao, T S.]]		[[Category: Chen, P]]
			[[Category: Cirl, C]]
			[[Category: Jiang, J S]]
			[[Category: Smith, T]]
			[[Category: Snyder, G A]]
			[[Category: Xiao, T S]]
	[[Category: Adapter protein]]		[[Category: Adapter protein]]
	[[Category: Beta-alpha-beta fold]]		[[Category: Beta-alpha-beta fold]]

OCA at 10:29, 24 April 2013

2013-04-24T10:29:15Z

← Older revision		Revision as of 10:29, 24 April 2013
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	{{STRUCTURE_4eo7\| PDB=4eo7 \| SCENE= }}		{{STRUCTURE_4eo7\| PDB=4eo7 \| SCENE= }}
	===Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.===		===Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.===
			{{ABSTRACT_PUBMED_23569230}}

	==Disease==		==Disease==

OCA at 22:41, 10 April 2013

2013-04-10T22:41:39Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+{{STRUCTURE_4eo7|  PDB=4eo7  |  SCENE=  }}
-The entry 4eo7 is ON HOLD  until Paper Publication
+==Disease==
-Authors: Snyder, G.A., Cirl, C., Jiang, J.S., Chen, P., Smith, T., Xiao, T.S.
+==Function==
-Description: Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.
+==About this Structure==

OCA at 08:49, 16 May 2012

2012-05-16T08:49:08Z

← Older revision		Revision as of 08:49, 16 May 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4eo7 is ON HOLD		The entry 4eo7 is ON HOLD until Paper Publication

	Authors: Snyder, G.A., Cirl, C., Jiang, J.S., Chen, P., Smith, T., Xiao, T.S.		Authors: Snyder, G.A., Cirl, C., Jiang, J.S., Chen, P., Smith, T., Xiao, T.S.

	Description: Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.		Description: Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.

OCA at 18:56, 2 May 2012

2012-05-02T18:56:44Z

← Older revision		Revision as of 18:56, 2 May 2012
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	The entry 4eo7 is ON HOLD		The entry 4eo7 is ON HOLD

	Authors: Snyder,G.A., Cirl, C., Jiang,J.S., Chen,P., Smith, T., Xiao,T.S.		Authors: Snyder, G.A., Cirl, C., Jiang, J.S., Chen, P., Smith, T., Xiao, T.S.

	Description: Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.		Description: Crystal structure of the TIR domain of human myeloid differentiation primary response protein 88.

OCA: Protected "4eo7" [edit=sysop:move=sysop]

2012-04-25T08:55:16Z

Protected "4eo7" [edit=sysop:move=sysop]

← Older revision	Revision as of 08:55, 25 April 2012
(No difference)