3pk1

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{{STRUCTURE_3pk1| PDB=3pk1 | SCENE= }}
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==Crystal structure of Mcl-1 in complex with the BaxBH3 domain==
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===Crystal structure of Mcl-1 in complex with the BaxBH3 domain===
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<StructureSection load='3pk1' size='340' side='right' caption='[[3pk1]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21199865}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3pk1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PK1 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pl7|3pl7]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=3pk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pk1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pk1 RCSB], [http://www.ebi.ac.uk/pdbsum/3pk1 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic activity of Bax, either directly through interactions with Bax or indirectly by sequestration of activator BH3-only proteins, or both. Mutations in Bax that promote apoptosis can provide insight into how Bax is regulated. Here, we describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-x(L) in complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These structures reveal canonical interactions between four signature hydrophobic amino acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival proteins. In both structures, Met-74 from the Bax peptide engages with the BH3-binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants disrupt interactions between Bax and all pro-survival proteins, but these Bax mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in colony assays even in the absence of an external apoptotic stimulus. These results support a model in which direct restraint of Bax by pro-survival Bcl-2 proteins is a barrier to apoptosis.
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==Function==
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Mutation to Bax beyond the BH3 domain disrupts interactions with pro-survival proteins and promotes apoptosis.,Czabotar PE, Lee EF, Thompson GV, Wardak AZ, Fairlie WD, Colman PM J Biol Chem. 2011 Mar 4;286(9):7123-31. Epub 2011 Jan 3. PMID:21199865<ref>PMID:21199865</ref>
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[[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/BAX_HUMAN BAX_HUMAN]] Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.<ref>PMID:8358790</ref> <ref>PMID:10772918</ref> <ref>PMID:8521816</ref> <ref>PMID:16113678</ref> <ref>PMID:18948948</ref> <ref>PMID:21199865</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3pk1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PK1 OCA].
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</div>
==See Also==
==See Also==
*[[Bcl-2|Bcl-2]]
*[[Bcl-2|Bcl-2]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021199865</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Colman, P M.]]
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[[Category: Colman, P M]]
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[[Category: Czabotar, P E.]]
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[[Category: Czabotar, P E]]
[[Category: Apoptosis-apoptosis regulator complex]]
[[Category: Apoptosis-apoptosis regulator complex]]
[[Category: Bax]]
[[Category: Bax]]

Revision as of 18:11, 21 December 2014

Crystal structure of Mcl-1 in complex with the BaxBH3 domain

3pk1, resolution 2.49Å

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