2kbw

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[[Image:2kbw.png|left|200px]]
 
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{{STRUCTURE_2kbw| PDB=2kbw | SCENE= }}
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==Solution Structure of human Mcl-1 complexed with human Bid_BH3 peptide==
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<StructureSection load='2kbw' size='340' side='right'caption='[[2kbw]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2kbw]] is a 2 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=2KBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBW FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kbw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kbw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Solution Structure of human Mcl-1 complexed with human Bid_BH3 peptide===
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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<ref>PMID:20392693</ref>
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{{ABSTRACT_PUBMED_20392693}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2kbw" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[2kbw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBW OCA].
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*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020392693</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Gehring, K.]]
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[[Category: Large Structures]]
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[[Category: Liu, Q.]]
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[[Category: Gehring K]]
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[[Category: Mansur-Azzam, N.]]
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[[Category: Liu Q]]
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[[Category: Matta-Camacho, E.]]
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[[Category: Mansur-Azzam N]]
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[[Category: Moldoveanu, T.]]
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[[Category: Matta-Camacho E]]
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[[Category: Sprules, T.]]
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[[Category: Moldoveanu T]]
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[[Category: Apoptosis]]
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[[Category: Sprules T]]
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[[Category: Bid_bh3]]
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[[Category: Complex]]
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[[Category: Developmental protein]]
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[[Category: Differentiation]]
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[[Category: Mcl-1]]
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[[Category: Membrane]]
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[[Category: Mitochondrion]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Transmembrane]]
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Current revision

Solution Structure of human Mcl-1 complexed with human Bid_BH3 peptide

PDB ID 2kbw

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