View source for 6vbz


==Crystal structure of the rat MLKL pseudokinase domain==
<StructureSection load='6vbz' size='340' side='right'caption='[[6vbz]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vbz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VBZ 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]] 2.192&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6vbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vbz OCA], [https://pdbe.org/6vbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vbz RCSB], [https://www.ebi.ac.uk/pdbsum/6vbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vbz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D3ZKP6_RAT D3ZKP6_RAT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The MLKL pseudokinase is the terminal effector in the necroptosis cell death pathway. Phosphorylation by its upstream regulator, RIPK3, triggers MLKL's conversion from a dormant cytoplasmic protein into oligomers that translocate to, and permeabilize, the plasma membrane to kill cells. The precise mechanisms underlying these processes are incompletely understood, and were proposed to differ between mouse and human cells. Here, we examine the divergence of activation mechanisms among nine vertebrate MLKL orthologues, revealing remarkable specificity of mouse and human RIPK3 for MLKL orthologues. Pig MLKL can restore necroptotic signaling in human cells; while horse and pig, but not rat, MLKL can reconstitute the mouse pathway. This selectivity can be rationalized from the distinct conformations observed in the crystal structures of horse and rat MLKL pseudokinase domains. These studies identify important differences in necroptotic signaling between species, and suggest that, more broadly, divergent regulatory mechanisms may exist among orthologous pseudoenzymes.

Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues.,Davies KA, Fitzgibbon C, Young SN, Garnish SE, Yeung W, Coursier D, Birkinshaw RW, Sandow JJ, Lehmann WIL, Liang LY, Lucet IS, Chalmers JD, Patrick WM, Kannan N, Petrie EJ, Czabotar PE, Murphy JM Nat Commun. 2020 Jun 19;11(1):3060. doi: 10.1038/s41467-020-16823-3. PMID:32561735<ref>PMID:32561735</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vbz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Czabotar PE]]
[[Category: Davies KA]]