View source for 7jw7


==Structure of monobody 27 human MLKL pseudokinase domain complex==
<StructureSection load='7jw7' size='340' side='right'caption='[[7jw7]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jw7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JW7 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]] 2.63&#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=7jw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jw7 OCA], [https://pdbe.org/7jw7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jw7 RCSB], [https://www.ebi.ac.uk/pdbsum/7jw7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jw7 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 ==
Phosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. While Monobody-32 constitutively binds the MLKL hinge region, Monobody-27 binds MLKL via an epitope that overlaps the RIPK3 binding site and is only exposed after phosphorylated MLKL disengages from RIPK3 following necroptotic stimulation. The crystal structures identified two distinct conformations of the MLKL pseudokinase domain, supporting the idea that a conformational transition accompanies MLKL disengagement from RIPK3. These studies provide further evidence that MLKL undergoes a large conformational change upon activation, and identify MLKL disengagement from RIPK3 as a key regulatory step in the necroptosis pathway.

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis.,Garnish SE, Meng Y, Koide A, Sandow JJ, Denbaum E, Jacobsen AV, Yeung W, Samson AL, Horne CR, Fitzgibbon C, Young SN, Smith PPC, Webb AI, Petrie EJ, Hildebrand JM, Kannan N, Czabotar PE, Koide S, Murphy JM Nat Commun. 2021 Apr 13;12(1):2211. doi: 10.1038/s41467-021-22400-z. PMID:33850121<ref>PMID:33850121</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7jw7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Czabotar PE]]
[[Category: Garnish SE]]
[[Category: Koide A]]
[[Category: Koide S]]
[[Category: Meng Y]]
[[Category: Murphy JM]]