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2rod

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Revision as of 06:58, 9 February 2016

Solution Structure of MCL-1 Complexed with NoxaA

Structural highlights

2rod is a 2 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1wsx, 2jm6, 2roc
Gene:	Mcl-1 (Mus musculus), Noxa (Mus musculus)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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. [APR_MOUSE] Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1 (By similarity). Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000 May 12;288(5468):1053-8. PMID:10807576
↑ Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005 Jun 1;19(11):1294-305. Epub 2005 May 18. PMID:15901672 doi:http://dx.doi.org/gad.1304105
↑ Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005 Feb 4;17(3):393-403. PMID:15694340 doi:S1097276505010403
↑ Akhtar RS, Geng Y, Klocke BJ, Latham CB, Villunger A, Michalak EM, Strasser A, Carroll SL, Roth KA. BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death. J Neurosci. 2006 Jul 5;26(27):7257-64. PMID:16822983 doi:http://dx.doi.org/10.1523/JNEUROSCI.0196-06.2006
↑ Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27. PMID:17389404
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rod"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]], [[2jm6|2jm6]], [[2roc|2roc]]</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]), Noxa ([http://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=2rod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rod OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rod RCSB], [http://www.ebi.ac.uk/pdbsum/2rod PDBsum]</span></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=2rod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rod OCA], [http://pdbe.org/2rod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rod RCSB], [http://www.ebi.ac.uk/pdbsum/2rod PDBsum]</span></td></tr>
 </table>
 == 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/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/APR_MOUSE APR_MOUSE]] Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1 (By similarity). Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1.<ref>PMID:10807576</ref> <ref>PMID:15901672</ref> <ref>PMID:15694340</ref> <ref>PMID:16822983</ref> <ref>PMID:17389404</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 17: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2rod ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2rod" style="background-color:#fffaf0;"></div>
 ==See Also==

2rod

From Proteopedia

Revision as of 06:58, 9 February 2016

Solution Structure of MCL-1 Complexed with NoxaA

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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