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==Structural basis of the specificity and interaction mechanism of Bmf binding to pro-survival proteins==
<StructureSection load='8iqm' size='340' side='right'caption='[[8iqm]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8iqm]] is a 2 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=8IQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IQM 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]] 1.967&#8491;</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=8iqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8iqm OCA], [https://pdbe.org/8iqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8iqm RCSB], [https://www.ebi.ac.uk/pdbsum/8iqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8iqm ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The apoptotic pathway is regulated by protein-protein interactions between members of the Bcl-2 family. Pro-survival Bcl-2 family proteins act as cell guardians and protect cells against death. Selective binding and neutralization of BH3-only proteins with pro-survival Bcl-2 family proteins is critical for initiating apoptosis. In this study, the binding assay shows that the BH3 peptide derived from the BH3-only protein Bmf has a high affinity for the pro-survival proteins Bcl-2 and Bcl-xL, but a much lower affinity for Mcl-1. The complex structures of Bmf BH3 with Bcl-2, Bcl-xL and Mcl-1 reveal that the alpha-helical Bmf BH3 accommodates into the canonical groove of these pro-survival proteins, but the conformational changes and some interactions are different among the three complexes. Bmf BH3 forms conserved hydrophobic and salt bridge interactions with Bcl-2 and Bcl-xL, and also establishes several hydrogen bonds to support their binding. However, the highly conserved Asp-Arg salt bridge is not formed in the Mcl-1/Bmf BH3 complex, and few hydrogen bonds are observed. Furthermore, mutational analysis shows that substitutions of less-conserved residues in the alpha2-alpha3 region of these pro-survival Bcl-2 family proteins, as well as the highly conserved Arg, lead to significant changes in their binding affinity to Bmf BH3, while substitutions of less-conserved residues in Bmf BH3 have a more dramatic effect on its affinity to Mcl-1. This study provides structural insight into the specificity and interaction mechanism of Bmf BH3 binding to pro-survival Bcl-2 family proteins, and helps guide the design of BH3 mimics targeting pro-survival Bcl-2 family proteins.

Structural basis of the specificity and interaction mechanism of Bmf binding to pro-survival Bcl-2 family proteins.,Wang H, Guo M, Wei H, Chen Y Comput Struct Biotechnol J. 2023 Jul 21;21:3760-3767. doi: , 10.1016/j.csbj.2023.07.017. eCollection 2023. PMID:37560128<ref>PMID:37560128</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8iqm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen Y]]
[[Category: Guo M]]
[[Category: Wang H]]
[[Category: Wei H]]