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[[Image:2nl9.gif|left|200px]]


{{Structure
==Crystal structure of the Mcl-1:Bim BH3 complex==
|PDB= 2nl9 |SIZE=350|CAPTION= <scene name='initialview01'>2nl9</scene>, resolution 1.550&Aring;
<StructureSection load='2nl9' size='340' side='right'caption='[[2nl9]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
<table><tr><td colspan='2'>[[2nl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NL9 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
|GENE= Mcl1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Rattus norvegicus and Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2nl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nl9 OCA], [https://pdbe.org/2nl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nl9 RCSB], [https://www.ebi.ac.uk/pdbsum/2nl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nl9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nl/2nl9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <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/main_output.php?pdb_ID=2nl9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


'''Crystal structure of the Mcl-1:Bim BH3 complex'''
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<ref>PMID:17389404</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2nl9" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
2NL9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus_and_homo_sapiens Rattus norvegicus and homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NL9 OCA].
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus and homo sapiens]]
[[Category: Mus musculus]]
[[Category: Colman, P M.]]
[[Category: Colman PM]]
[[Category: Czabotar, P E.]]
[[Category: Czabotar PE]]
[[Category: CL]]
[[Category: ZN]]
[[Category: apoptosis]]
[[Category: bcl-2]]
[[Category: bim]]
[[Category: mcl-1]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:47:51 2008''

Latest revision as of 11:20, 30 October 2024

Crystal structure of the Mcl-1:Bim BH3 complexCrystal structure of the Mcl-1:Bim BH3 complex

Structural highlights

2nl9 is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.55Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B2L11_HUMAN Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.[1] [2] [3] [4] [5] [6]

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[7]

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

See Also

References

  1. ↑ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95. PMID:9430630 doi:http://dx.doi.org/10.1093/emboj/17.2.384
  2. ↑ U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41. PMID:11734221
  3. ↑ Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002 May 15;62(10):2976-81. PMID:12019181
  4. ↑ Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002 Jun;22(11):3577-89. PMID:11997495
  5. ↑ Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM. Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61. PMID:15147734 doi:http://dx.doi.org/10.1016/j.biocel.2003.12.015
  6. ↑ Fukazawa H, Noguchi K, Masumi A, Murakami Y, Uehara Y. BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther. 2004 Oct;3(10):1281-8. PMID:15486195
  7. ↑ 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

2nl9, resolution 1.55Å

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