View source for 7mon


==Structure of human RIPK3-MLKL complex==
<StructureSection load='7mon' size='340' side='right'caption='[[7mon]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mon]] is a 2 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=7MON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MON 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]] 2.23&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZL1:N-[4-({2-[(cyclopropanecarbonyl)amino]pyridin-4-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide'>ZL1</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=7mon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mon OCA], [https://pdbe.org/7mon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mon RCSB], [https://www.ebi.ac.uk/pdbsum/7mon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mon ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL.

Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis.,Meng Y, Davies KA, Fitzgibbon C, Young SN, Garnish SE, Horne CR, Luo C, Garnier JM, Liang LY, Cowan AD, Samson AL, Lessene G, Sandow JJ, Czabotar PE, Murphy JM Nat Commun. 2021 Nov 22;12(1):6783. doi: 10.1038/s41467-021-27032-x. PMID:34811356<ref>PMID:34811356</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mon" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Czabotar PE]]
[[Category: Davies KA]]
[[Category: Meng Y]]
[[Category: Murphy JM]]