View source for 7l6w


==SFX structure of the MyD88 TIR domain higher-order assembly==
<StructureSection load='7l6w' size='340' side='right'caption='[[7l6w]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7l6w]] 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=7L6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L6W FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=7l6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l6w OCA], [https://pdbe.org/7l6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l6w RCSB], [https://www.ebi.ac.uk/pdbsum/7l6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l6w ProSAT]</span></td></tr>
</table>
== 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> 
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL(TIR)) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88(TIR)). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88(TIR) assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MAL(TIR). We demonstrate via mutagenesis that the MyD88(TIR) assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88(TIR). Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques.

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.,Clabbers MTB, Holmes S, Muusse TW, Vajjhala PR, Thygesen SJ, Malde AK, Hunter DJB, Croll TI, Flueckiger L, Nanson JD, Rahaman MH, Aquila A, Hunter MS, Liang M, Yoon CH, Zhao J, Zatsepin NA, Abbey B, Sierecki E, Gambin Y, Stacey KJ, Darmanin C, Kobe B, Xu H, Ve T Nat Commun. 2021 May 10;12(1):2578. doi: 10.1038/s41467-021-22590-6. PMID:33972532<ref>PMID:33972532</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7l6w" 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: Abbey B]]
[[Category: Aquila A]]
[[Category: Clabbers MTB]]
[[Category: Croll TI]]
[[Category: Darmanin C]]
[[Category: Flueckiger L]]
[[Category: Gambin Y]]
[[Category: Holmes S]]
[[Category: Hunter DJB]]
[[Category: Hunter MS]]
[[Category: Kobe B]]
[[Category: Liang M]]
[[Category: Malde AK]]
[[Category: Muusse TW]]
[[Category: Nanson JD]]
[[Category: Rahaman MH]]
[[Category: Sierecki E]]
[[Category: Stacey KJ]]
[[Category: Thygesen SJ]]
[[Category: Vajjhala P]]
[[Category: Ve T]]
[[Category: Xu H]]
[[Category: Yoon CH]]
[[Category: Zatsepin NA]]
[[Category: Zhao J]]