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| | ==Solution Structure of human Mcl-1 complexed with human Bid_BH3 peptide== | | ==Solution Structure of human Mcl-1 complexed with human Bid_BH3 peptide== |
| - | <StructureSection load='2kbw' size='340' side='right' caption='[[2kbw]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2kbw' size='340' side='right'caption='[[2kbw]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kbw]] is a 2 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=2KBW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KBW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kbw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]]</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]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, Myeloid Cell Leukemia 1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, Myeloid Cell Leukemia 1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BID ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbw OCA], [http://pdbe.org/2kbw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kbw RCSB], [http://www.ebi.ac.uk/pdbsum/2kbw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbw 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=2kbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbw OCA], [https://pdbe.org/2kbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kbw RCSB], [https://www.ebi.ac.uk/pdbsum/2kbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> [[http://www.uniprot.org/uniprot/BID_HUMAN BID_HUMAN]] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.<ref>PMID:14583606</ref> | + | [[https://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> [[https://www.uniprot.org/uniprot/BID_HUMAN BID_HUMAN]] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.<ref>PMID:14583606</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/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Gehring, K]] | | [[Category: Gehring, K]] |
| | [[Category: Liu, Q]] | | [[Category: Liu, Q]] |
| Structural highlights
Function
[MCL1_HUMAN] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.[1] [BID_HUMAN] The major proteolytic product p15 BID allows the release of cytochrome c (By similarity). Isoform 1, isoform 2 and isoform 4 induce ICE-like proteases and apoptosis. Isoform 3 does not induce apoptosis. Counters the protective effect of Bcl-2.[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
Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic BCL-2 family member active in the preservation of mitochondrial integrity during apoptosis, has fundamental roles in development and hematopoiesis and is dysregulated in human cancers. It bears a unique, intrinsically unstructured, N-terminal sequence, which leads to its instability in cells and hinders protein production and structural characterization. Here, we present collective data from NMR spectroscopy and titration calorimetry to reveal the selectivity of MCL-1 in binding BCL-2 homology 3 (BH3) ligands of interest for mammalian biology. The N-terminal sequence weakens the BH3 interactions but does not affect selectivity. Its removal by calpain-mediated limited proteolysis results in a stable BCL-2-like core domain of MCL-1 (cMCL-1). This core is necessary and sufficient for BH3 ligand binding. Significantly, we also characterized the in vitro protein-protein interaction between cMCL-1 and activated BID by size exclusion chromatography and NMR titrations. This interaction occurs in a very slow manner in solution but is otherwise similar to the interaction between cMCL-1 and BID-BH3 peptides. We also present the solution structure of complex cMCL-1xhBID-BH3, which completes the family portrait of MCL-1 complexes and may facilitate drug discovery against human tumors.
Apoptotic regulation by MCL-1 through heterodimerization.,Liu Q, Moldoveanu T, Sprules T, Matta-Camacho E, Mansur-Azzam N, Gehring K J Biol Chem. 2010 Jun 18;285(25):19615-24. Epub 2010 Apr 14. PMID:20392693[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK. Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46. PMID:10766760 doi:10.1074/jbc.M909572199
- ↑ Renshaw SA, Dempsey CE, Barnes FA, Bagstaff SM, Dower SK, Bingle CD, Whyte MK. Three novel Bid proteins generated by alternative splicing of the human Bid gene. J Biol Chem. 2004 Jan 23;279(4):2846-55. Epub 2003 Oct 28. PMID:14583606 doi:http://dx.doi.org/10.1074/jbc.M309769200
- ↑ Liu Q, Moldoveanu T, Sprules T, Matta-Camacho E, Mansur-Azzam N, Gehring K. Apoptotic regulation by MCL-1 through heterodimerization. J Biol Chem. 2010 Jun 18;285(25):19615-24. Epub 2010 Apr 14. PMID:20392693 doi:10.1074/jbc.M110.105452
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