View source for 8slz


==Crystal structure of phosphorylated (T357/S358) human MLKL pseudokinase domain==
<StructureSection load='8slz' size='340' side='right'caption='[[8slz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8slz]] 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=8SLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SLZ 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='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></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=8slz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8slz OCA], [https://pdbe.org/8slz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8slz RCSB], [https://www.ebi.ac.uk/pdbsum/8slz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8slz 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 necroptosis pathway is a lytic, pro-inflammatory mode of cell death that is widely implicated in human disease, including renal, pulmonary, gut and skin inflammatory pathologies. The precise mechanism of the terminal steps in the pathway, where the RIPK3 kinase phosphorylates and triggers a conformation change and oligomerization of the terminal pathway effector, MLKL, are only emerging. Here, we structurally identify RIPK3-mediated phosphorylation of the human MLKL activation loop as a cue for MLKL pseudokinase domain dimerization. MLKL pseudokinase domain dimerization subsequently drives formation of elongated homotetramers. Negative stain electron microscopy and modelling support nucleation of the MLKL tetramer assembly by a central coiled coil formed by the extended, ~80 A brace helix that connects the pseudokinase and executioner four-helix bundle domains. Mutational data assert MLKL tetramerization as an essential prerequisite step to enable the release and reorganization of four-helix bundle domains for membrane permeabilization and cell death.

Phosphorylation-dependent pseudokinase domain dimerization drives full-length MLKL oligomerization.,Meng Y, Garnish SE, Davies KA, Black KA, Leis AP, Horne CR, Hildebrand JM, Hoblos H, Fitzgibbon C, Young SN, Dite T, Dagley LF, Venkat A, Kannan N, Koide A, Koide S, Glukhova A, Czabotar PE, Murphy JM Nat Commun. 2023 Oct 26;14(1):6804. doi: 10.1038/s41467-023-42255-w. PMID:37884510<ref>PMID:37884510</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8slz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Czabotar PE]]
[[Category: Davies KA]]
[[Category: Meng Y]]
[[Category: Murphy JM]]