View source for 4btf


==Structure of MLKL==
<StructureSection load='4btf' size='340' side='right'caption='[[4btf]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4btf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4btf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btf OCA], [http://pdbe.org/4btf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4btf RCSB], [http://www.ebi.ac.uk/pdbsum/4btf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4btf ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/MLKL_MOUSE MLKL_MOUSE]] Required for the execution of programmed necrosis (By similarity). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mixed lineage kinase domain-like (MLKL) is a component of the "necrosome," the multiprotein complex that triggers tumor necrosis factor (TNF)-induced cell death by necroptosis. To define the specific role and molecular mechanism of MLKL action, we generated MLKL-deficient mice and solved the crystal structure of MLKL. Although MLKL-deficient mice were viable and displayed no hematopoietic anomalies or other obvious pathology, cells derived from these animals were resistant to TNF-induced necroptosis unless MLKL expression was restored. Structurally, MLKL comprises a four-helical bundle tethered to the pseudokinase domain, which contains an unusual pseudoactive site. Although the pseudokinase domain binds ATP, it is catalytically inactive and its essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation. Structure-guided mutation of the MLKL pseudoactive site resulted in constitutive, RIPK3-independent necroptosis, demonstrating that modification of MLKL is essential for propagation of the necroptosis pathway downstream of RIPK3.

The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism.,Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS Immunity. 2013 Sep 4. pii: S1074-7613(13)00348-8. doi:, 10.1016/j.immuni.2013.06.018. PMID:24012422<ref>PMID:24012422</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4btf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pseudoenzyme|Pseudoenzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Czabotar, P E]]
[[Category: Murphy, J M]]
[[Category: Necroptosis]]
[[Category: Pseduokinase]]
[[Category: Transferase]]