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| | ==Solution structure of Mcl-1 Complexed with Puma== | | ==Solution structure of Mcl-1 Complexed with Puma== |
| - | <StructureSection load='2roc' size='340' side='right' caption='[[2roc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2roc' size='340' side='right'caption='[[2roc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2roc]] 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=2ROC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ROC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2roc]] 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=2ROC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ROC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]], [[2jm6|2jm6]], [[2rod|2rod]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wsx|1wsx]], [[2jm6|2jm6]], [[2rod|2rod]]</div></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]), Puma ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mcl-1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Puma ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2roc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2roc OCA], [http://pdbe.org/2roc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2roc RCSB], [http://www.ebi.ac.uk/pdbsum/2roc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2roc 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=2roc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2roc OCA], [https://pdbe.org/2roc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2roc RCSB], [https://www.ebi.ac.uk/pdbsum/2roc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2roc ProSAT]</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/BBC3_MOUSE BBC3_MOUSE]] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (By similarity). Regulates ER stress-induced neuronal apoptosis.<ref>PMID:21159964</ref> <ref>PMID:22761832</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. [[https://www.uniprot.org/uniprot/BBC3_MOUSE BBC3_MOUSE]] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (By similarity). Regulates ER stress-induced neuronal apoptosis.<ref>PMID:21159964</ref> <ref>PMID:22761832</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[B-cell lymphoma protein|B-cell lymphoma protein]] | + | *[[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, C L]] |
| 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. [BBC3_MOUSE] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (By similarity). Regulates ER stress-induced neuronal apoptosis.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Galehdar Z, Swan P, Fuerth B, Callaghan SM, Park DS, Cregan SP. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci. 2010 Dec 15;30(50):16938-48. doi: 10.1523/JNEUROSCI.1598-10.2010. PMID:21159964 doi:http://dx.doi.org/10.1523/JNEUROSCI.1598-10.2010
- ↑ Ghosh AP, Klocke BJ, Ballestas ME, Roth KA. CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS One. 2012;7(6):e39586. doi: 10.1371/journal.pone.0039586. Epub 2012 Jun 28. PMID:22761832 doi:http://dx.doi.org/10.1371/journal.pone.0039586
- ↑ 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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