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| | ==Solution structure of MCL-1== | | ==Solution structure of MCL-1== |
| - | <StructureSection load='1wsx' size='340' side='right'caption='[[1wsx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1wsx' size='340' side='right'caption='[[1wsx]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1wsx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WSX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1wsx]] is a 1 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=1WSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WSX FirstGlance]. <br> |
| - | </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 LK3 transgenic mice])</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'>[https://proteopedia.org/fgij/fg.htm?mol=1wsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wsx OCA], [https://pdbe.org/1wsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wsx RCSB], [https://www.ebi.ac.uk/pdbsum/1wsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wsx 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=1wsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wsx OCA], [https://pdbe.org/1wsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wsx RCSB], [https://www.ebi.ac.uk/pdbsum/1wsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wsx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/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]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Chen, L]] | + | [[Category: Chen L]] |
| - | [[Category: Day, C L]] | + | [[Category: Day CL]] |
| - | [[Category: Harrison, P J]] | + | [[Category: Harrison PJ]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Huang, D C]] | + | [[Category: Huang DC]] |
| - | [[Category: Richardson, S J]] | + | [[Category: Richardson SJ]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2]]
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| - | [[Category: Bh3]]
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| - | [[Category: Helical bundle]]
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| - | [[Category: Mcl-1]]
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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
The B cell lymphoma-2 (Bcl-2) homologs myeloid cell leukemia-1 (Mcl-1) and A1 are prosurvival factors that selectively bind a subset of proapoptotic Bcl homology (BH) 3-only proteins. To investigate the molecular basis of the selectivity, we determined the solution structure of the C-terminal Bcl-2-like domain of Mcl-1. This domain shares features expected of a prosurvival Bcl-2 protein, having a helical fold centered on a core hydrophobic helix and a surface-exposed hydrophobic groove for binding its cognate partners. A number of residues in the binding groove differentiate Mcl-1 from its homologs, and in contrast to other Bcl-2 homologs, Mcl-1 has a binding groove in a conformation intermediate between the open structures characterized by peptide complexes and the closed state observed in unliganded structures. Mutagenesis of potential binding site residues was used to probe the contributions of groove residues to the binding properties of Mcl-1. Although mutations in Mcl-1 had little impact on binding, a single mutation in the BH3-only ligand Bad enabled it to bind both Mcl-1 and A1 while retaining its binding to Bcl-2, Bcl-xL, and Bcl-w. Elucidating the selective action of certain BH3-only ligands is required for delineating their mode of action and will aid the search for effective BH3-mimetic drugs.
Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands.,Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG J Biol Chem. 2005 Feb 11;280(6):4738-44. Epub 2004 Nov 18. PMID:15550399[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem. 2005 Feb 11;280(6):4738-44. Epub 2004 Nov 18. PMID:15550399 doi:http://dx.doi.org/10.1074/jbc.M411434200
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