5le2: Difference between revisions
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==Crystal structure of DARPin-DARPin rigid fusion, variant DDD_D12_15_D12_15_D12== | ==Crystal structure of DARPin-DARPin rigid fusion, variant DDD_D12_15_D12_15_D12== | ||
<StructureSection load='5le2' size='340' side='right' caption='[[5le2]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='5le2' size='340' side='right'caption='[[5le2]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5le2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5le2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LE2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=5le2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5le2 OCA], [https://pdbe.org/5le2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5le2 RCSB], [https://www.ebi.ac.uk/pdbsum/5le2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5le2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Multivalent binding proteins can gain biological activities beyond what is inherent in the individual binders, by bringing together different target molecules, restricting their conformational flexibility or changing their subcellular localization. In this study, we demonstrate a method to build up rigid multivalent and multispecific scaffolds by exploiting the modular nature of a repeat protein scaffold and avoiding flexible linkers. We use DARPins (Designed Ankyrin Repeat Proteins), synthetic binding proteins based on the Ankyrin-repeat protein scaffold, as binding units. Their ease of in vitro selection, high production yield and stability make them ideal specificity-conferring building blocks for the design of more complex constructs. C- and N-terminal DARPin capping repeats were re-designed to be joined by a shared helix in such a way that rigid connector modules are formed. This allows us to join two or more DARPins in predefined geometries without compromising their binding affinities and specificities. Nine connector modules with distinct geometries were designed; for eight of these we were able to confirm the structure by X-ray crystallography, while only one did not crystallize. The bispecific constructs were all able to bind both target proteins simultaneously. | |||
Rigidly connected multispecific artificial binders with adjustable geometries.,Wu Y, Batyuk A, Honegger A, Brandl F, Mittl PRE, Pluckthun A Sci Rep. 2017 Sep 11;7(1):11217. doi: 10.1038/s41598-017-11472-x. PMID:28894181<ref>PMID:28894181</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5le2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Synthetic construct | [[Category: Large Structures]] | ||
[[Category: Batyuk | [[Category: Synthetic construct]] | ||
[[Category: Mittl | [[Category: Batyuk A]] | ||
[[Category: Plueckthun | [[Category: Mittl PR]] | ||
[[Category: Wu | [[Category: Plueckthun A]] | ||
[[Category: Wu Y]] | |||