9ot8: Difference between revisions
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==Crystal structure of Galectin-3 bound to FN3con-9 and FN3con-41, a cooperative binder that recognises the Galectin-3-FN3con-9 interface== | |||
<StructureSection load='9ot8' size='340' side='right'caption='[[9ot8]], [[Resolution|resolution]] 1.96Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ot8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9OT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OT8 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]] 1.96Å</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=9ot8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ot8 OCA], [https://pdbe.org/9ot8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ot8 RCSB], [https://www.ebi.ac.uk/pdbsum/9ot8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ot8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LEG3_HUMAN LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.<ref>PMID:15181153</ref> <ref>PMID:19594635</ref> <ref>PMID:19616076</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein biosensors are important tools in research, bioengineering, and diagnostics. Unlike fully integrated single-component biosensors, two-component biosensors are modular and can be rapidly adapted to new targets by replacing binding elements. However, their utility is limited by a "hook effect," where high analyte concentrations lead to dissociation of the signalling complex and signal loss. We address this challenge by utilizing sequential mRNA display selection campaigns to develop high-affinity, cooperative FN3con (monobody) binding domains to Galectin-3, a protein biomarker of heart failure. Two-component biosensors equipped with such cooperative binders were devoid of the hook effect and demonstrated 5-fold higher sensitivity to Galectin-3 compared to systems based on non-cooperative binding domains. High-resolution crystal structures of cooperative and non-cooperative binding domains revealed how interactions between the two domains establish a cooperative Galectin-3 binding interface. The results and experimental approaches presented in this work enable the construction of high-performance biosensors for diverse applications. | |||
Cooperative Binding Domains Enhance Sensitivity and Overcome the Hook Effect in Two-Component Protein Biosensors.,Mutschler R, Caputo AT, Guo Z, Fiorito MM, Hayat IF, Newton S, Zhang X, Karunathilaka N, Duval C, Brazel H, Chan W, Kostner K, Korczyk D, Abankwa DK, Atherton JJ, Coats AJS, Punyadeera C, Alexandrov K, Cui Z ACS Sens. 2026 Mar 27;11(3):2870-2879. doi: 10.1021/acssensors.6c00488. Epub 2026 , Mar 9. PMID:41801969<ref>PMID:41801969</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ot8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Abwanka D]] | |||
[[Category: Alexandrov K]] | |||
[[Category: Brazel H]] | |||
[[Category: Caputo AT]] | |||
[[Category: Cui Z]] | |||
[[Category: Duval C]] | |||
[[Category: Fiorito MM]] | |||
[[Category: Guo Z]] | |||
[[Category: Karunathilaka N]] | |||
[[Category: Mutschler R]] | |||
[[Category: Newton S]] | |||
[[Category: Punyadeera C]] | |||
[[Category: Zhang X]] | |||
