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| | ==Solution Structure of MCL-1 Complexed with NoxaA== | | ==Solution Structure of MCL-1 Complexed with NoxaA== |
| - | <StructureSection load='2rod' size='340' side='right' caption='[[2rod]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2rod' size='340' side='right'caption='[[2rod]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ROD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ROD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rod]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ROD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ROD FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]], [[2jm6|2jm6]], [[2roc|2roc]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mcl-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Noxa ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=2rod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rod OCA], [https://pdbe.org/2rod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rod RCSB], [https://www.ebi.ac.uk/pdbsum/2rod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rod ProSAT]</span></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=2rod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rod OCA], [http://pdbe.org/2rod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rod RCSB], [http://www.ebi.ac.uk/pdbsum/2rod PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCL1_MOUSE MCL1_MOUSE]] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. [[http://www.uniprot.org/uniprot/APR_MOUSE APR_MOUSE]] Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1 (By similarity). Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1.<ref>PMID:10807576</ref> <ref>PMID:15901672</ref> <ref>PMID:15694340</ref> <ref>PMID:16822983</ref> <ref>PMID:17389404</ref> | + | [https://www.uniprot.org/uniprot/MCL1_MOUSE MCL1_MOUSE] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ro/2rod_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ro/2rod_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[Bcl-2|Bcl-2]] | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Day, C L]] | + | [[Category: Day CL]] |
| - | [[Category: Fairlie, W D]] | + | [[Category: Fairlie WD]] |
| - | [[Category: Fan, F C]] | + | [[Category: Fan FC]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Lee, E F]] | + | [[Category: Lee EF]] |
| - | [[Category: Smits, C]] | + | [[Category: Smits C]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2]]
| + | |
| - | [[Category: Bh3-only]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Differentiation]]
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| - | [[Category: Mcl-1]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Noxaa]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
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| - | [[Category: Transmembrane]]
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| Structural highlights
Function
MCL1_MOUSE Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pro-survival proteins in the B-cell lymphoma-2 (Bcl-2) family have a defined specificity profile for their cell death-inducing BH3-only antagonists. Solution structures of myeloid cell leukaemia-1 (Mcl-1) in complex with the BH3 domains from Noxa and Puma, two proteins regulated by the tumour suppressor p53, show that they bind as amphipathic alpha-helices in the same hydrophobic groove of Mcl-1, using conserved residues for binding. Thermodynamic parameters for the interaction of Noxa, Puma and the related BH3 domains of Bmf, Bim, Bid and Bak with Mcl-1 were determined by calorimetry. These unstructured BH3 domains bind Mcl-1 with affinities that span 3 orders of magnitude, and binding is an enthalpically driven and entropy-enthalpy-compensated process. Alanine scanning analysis of Noxa demonstrated that only a subset of residues is required for interaction with Mcl-1, and these residues are localised to a short highly conserved sequence motif that defines the BH3 domain. Chemical shift mapping of Mcl-1:BH3 complexes showed that Mcl-1 engages all BH3 ligands in a similar way and that, in addition to changes in the immediate vicinity of the binding site, small molecule-wide structural adjustments accommodate ligand binding. Our studies show that unstructured peptides, such as the BH3 domains, behave like their structured counterparts and can bind tightly and selectively in an enthalpically driven process.
Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1.,Day CL, Smits C, Fan FC, Lee EF, Fairlie WD, Hinds MG J Mol Biol. 2008 Jul 25;380(5):958-71. Epub 2008 Jun 4. PMID:18589438[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Day CL, Smits C, Fan FC, Lee EF, Fairlie WD, Hinds MG. Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. J Mol Biol. 2008 Jul 25;380(5):958-71. Epub 2008 Jun 4. PMID:18589438 doi:10.1016/j.jmb.2008.05.071
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