View source for 4cim


==Complex of a Bcl-w BH3 mutant with a BH3 domain==
<StructureSection load='4cim' size='340' side='right'caption='[[4cim]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cim]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CIM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cim OCA], [https://pdbe.org/4cim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cim RCSB], [https://www.ebi.ac.uk/pdbsum/4cim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cim ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B2CL2_HUMAN B2CL2_HUMAN] Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.<ref>PMID:8761287</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bcl-2 Homology 3 (BH3) domains are short sequence motifs that mediate nearly all protein-protein interactions between B cell lymphoma 2 (Bcl-2) family proteins in the intrinsic apoptotic cell death pathway. These sequences are found on both pro-survival and pro-apoptotic members even though their primary function is believed to be associated with induction of cell death. Here, we identify critical features of the BH3 domains of pro-survival proteins that distinguish them functionally from their pro-apoptotic counterparts. Biochemical and X-ray crystallographic studies demonstrate that these differences reduce the capacity of most pro-survival proteins to form high affinity "BH3-in-groove" complexes that are critical for cell death induction. Switching these residues for the corresponding residues in Bcl-2 homologous antagonist/killer (Bak) increases the binding affinity of isolated BH3 domains to pro-survival proteins, however, their exchange in the context of the parental protein causes rapid proteasomal degradation due to protein destabilization. This is supported by further X-ray crystallographic studies that capture elements of this destabilization in one pro-survival protein, Bcl-w. In pro-apoptotic Bak, we demonstrate that the corresponding distinguishing residues are important for its stability, cell-killing capacity, and antagonism by pro-survival proteins.

The Functional Differences of Pro-survival and Pro-apoptotic B cell lymphoma 2 (Bcl-2) Proteins Depend on Structural Differences in their Bcl-2 Homology 3 (BH3) Domains.,Lee EF, Dewson G, Evangelista M, Pettikiriarachchi A, Zhu H, Colman PM, Fairlie WD J Biol Chem. 2014 Nov 3. pii: jbc.M114.610758. PMID:25371206<ref>PMID:25371206</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cim" style="background-color:#fffaf0;"></div>

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Colman PM]]
[[Category: Fairlie WD]]
[[Category: Lee EF]]