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| | ==Crystal structure of the human MLKL kinase-like domain== | | ==Crystal structure of the human MLKL kinase-like domain== |
| - | <StructureSection load='4m67' size='340' side='right' caption='[[4m67]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4m67' size='340' side='right'caption='[[4m67]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m67]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M67 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M67 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m67]] 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=4M67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M67 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m66|4m66]], [[4m68|4m68]], [[4m69|4m69]]</td></tr> | + | </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=4m67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m67 OCA], [https://pdbe.org/4m67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m67 RCSB], [https://www.ebi.ac.uk/pdbsum/4m67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m67 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLKL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4m67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m67 OCA], [http://pdbe.org/4m67 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m67 RCSB], [http://www.ebi.ac.uk/pdbsum/4m67 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m67 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN]] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Peng, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Shi, Y]] | + | [[Category: Peng W]] |
| - | [[Category: Wu, J]] | + | [[Category: Shi Y]] |
| - | [[Category: Xie, T]] | + | [[Category: Wu J]] |
| - | [[Category: Yan, C]] | + | [[Category: Xie T]] |
| - | [[Category: A substrate of rip3]]
| + | [[Category: Yan C]] |
| - | [[Category: Kinase-like]]
| + | |
| - | [[Category: Rip3]]
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| - | [[Category: Signaling protein]]
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| Structural highlights
Function
MLKL_HUMAN Required for the execution of programmed necrosis.[1]
Publication Abstract from PubMed
RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the alphaC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling.
Structural Insights into RIP3-Mediated Necroptotic Signaling.,Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y Cell Rep. 2013 Oct 17;5(1):70-8. doi: 10.1016/j.celrep.2013.08.044. Epub 2013 Oct, 3. PMID:24095729[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012 Jan 20;148(1-2):228-43. doi: 10.1016/j.cell.2011.11.030. PMID:22265414 doi:http://dx.doi.org/10.1016/j.cell.2011.11.030
- ↑ Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y. Structural Insights into RIP3-Mediated Necroptotic Signaling. Cell Rep. 2013 Oct 17;5(1):70-8. doi: 10.1016/j.celrep.2013.08.044. Epub 2013 Oct, 3. PMID:24095729 doi:http://dx.doi.org/10.1016/j.celrep.2013.08.044
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