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| ==Solution structure of the MLKL N-terminal domain== | | ==Solution structure of the MLKL N-terminal domain== |
| <StructureSection load='2msv' size='340' side='right' caption='[[2msv]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | | <StructureSection load='2msv' size='340' side='right'caption='[[2msv]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2msv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MSV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MSV FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2msv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MSV FirstGlance]. <br> |
| </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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2msv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2msv OCA], [http://pdbe.org/2msv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2msv RCSB], [http://www.ebi.ac.uk/pdbsum/2msv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2msv ProSAT]</span></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=2msv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2msv OCA], [https://pdbe.org/2msv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2msv RCSB], [https://www.ebi.ac.uk/pdbsum/2msv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2msv 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;">
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| == Publication Abstract from PubMed ==
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| MLKL is crucial for necroptosis, permeabilizing membranes through its N-terminal region upon phosphorylation of its kinase-like domain by RIP3. However, the mechanism underlying membrane permeabilization is unknown. The solution structure of the MLKL N-terminal region determined by nuclear magnetic resonance spectroscopy reveals a four-helix bundle with an additional helix at the top that is likely key for MLKL function, and a sixth, C-terminal helix that interacts with the top helix and with a poorly packed interface within the four-helix bundle. Fluorescence spectroscopy measurements indicate that much of the four-helix bundle inserts into membranes, but not the C-terminal helix. Moreover, we find that the four-helix bundle is sufficient to induce liposome leakage and that the C-terminal helix inhibits this activity. These results suggest that the four-helix bundle mediates membrane breakdown during necroptosis and that the sixth helix acts as a plug that prevents opening of the bundle and is released upon RIP3 phosphorylation.
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| A Plug Release Mechanism for Membrane Permeation by MLKL.,Su L, Quade B, Wang H, Sun L, Wang X, Rizo J Structure. 2014 Oct 7;22(10):1489-500. doi: 10.1016/j.str.2014.07.014. Epub 2014 , Sep 11. PMID:25220470<ref>PMID:25220470</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 2msv" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Quade, B]] | | [[Category: Large Structures]] |
| [[Category: Rizo, J]] | | [[Category: Quade B]] |
| [[Category: Su, L]] | | [[Category: Rizo J]] |
| [[Category: Sun, L]] | | [[Category: Su L]] |
| [[Category: Wang, H]] | | [[Category: Sun L]] |
| [[Category: Wang, X]] | | [[Category: Wang H]] |
| [[Category: Membrane pore]]
| | [[Category: Wang X]] |
| [[Category: Membrane protein]]
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