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2nla

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Revision as of 19:03, 25 December 2014

Crystal structure of the Mcl-1:mNoxaB BH3 complex

Structural highlights

2nla is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1wsx, 2nl9
Gene:	Mcl1 (Homo sapiens)
Resources:	FirstGlance, OCA, 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

Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.

Structural insights into the degradation of Mcl-1 induced by BH3 domains.,Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27. PMID:17389404^[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
↑ 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

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/2nla"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2nla]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NLA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NLA FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]], [[2nl9|2nl9]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wsx|1wsx]], [[2nl9|2nl9]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mcl1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mcl1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nla OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2nla RCSB], [http://www.ebi.ac.uk/pdbsum/2nla 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=2nla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nla OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2nla RCSB], [http://www.ebi.ac.uk/pdbsum/2nla PDBsum]</span></td></tr>
-<table>
+</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/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 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Colman, P M.]]
+[[Category: Colman, P M]]
-[[Category: Czabotar, P E.]]
+[[Category: Czabotar, P E]]
 [[Category: Apoptosis]]
 [[Category: Bcl-2]]
 [[Category: Mcl-1]]
 [[Category: Noxa]]

2nla

From Proteopedia

Revision as of 19:03, 25 December 2014

Crystal structure of the Mcl-1:mNoxaB BH3 complex

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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