View source for 6stj


==Selective Affimers Recognize BCL-2 Family Proteins Through Non-Canonical Structural Motifs==
<StructureSection load='6stj' size='340' side='right'caption='[[6stj]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6stj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saltans_group Saltans group]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6STJ 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]] 2.2&#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=6stj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6stj OCA], [https://pdbe.org/6stj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6stj RCSB], [https://www.ebi.ac.uk/pdbsum/6stj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6stj 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 BCL-2 family is a challenging group of proteins to target selectively due to sequence and structural homologies across the family. Selective ligands for the BCL-2 family regulators of apoptosis are useful as probes to understand cell biology and apoptotic signalling pathways, and as starting points for inhibitor design. We have used phage display to isolate Affimer reagents (non-antibody binding proteins based on a conserved scaffold) to identify ligands for MCL-1, BCL-xL, BCL-2, BAK and BAX, then used multiple biophysical characterisation methods to probe the interactions. We established that purified Affimers elicit selective recognition of their target BCL-2 protein. For anti-apoptotic targets BCL-xL and MCL-1, competitive inhibition of their canonical protein-protein interactions is demonstrated. Co-crystal structures reveal an unprecedented mode of molecular recognition; where a BH3 helix is normally bound, flexible loops from the Affimer dock into the BH3 binding cleft. Moreover, the Affimers induce a change in the target proteins towards a desirable drug bound like conformation. These proof of concept studies indicate that Affimers could be used as alternative templates to inspire design of selective BCL-2 family modulators and more generally other protein-protein interaction inhibitors.

Selective Affimers Recognize the BCL-2 Family Proteins BCL-xL and MCL-1 through Non-Canonical Structural Motifs.,Miles J, Hobor F, Trinh C, Taylor J, Tiede C, Rowell P, Jackson B, Nadat F, Ramsahye P, Kyle H, Wicky B, Clarke J, Tomlinson D, Wilson A, Edwards T Chembiochem. 2020 Sep 22. doi: 10.1002/cbic.202000585. PMID:32961017<ref>PMID:32961017</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6stj" 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: Saltans group]]
[[Category: Clarke J]]
[[Category: Edwards TA]]
[[Category: Hobor F]]
[[Category: Jackson B]]
[[Category: Kyle HF]]
[[Category: Miles JA]]
[[Category: Nadat F]]
[[Category: Rowell PR]]
[[Category: Taylor J]]
[[Category: Tiede C]]
[[Category: Tomlinson DC]]
[[Category: Trinh CH]]
[[Category: Wicky BIM]]
[[Category: Wilson AJ]]