8x0t: Difference between revisions
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The | ==Frizzled8 CRD in complex with pF8_AC3 Fab== | ||
<StructureSection load='8x0t' size='340' side='right'caption='[[8x0t]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8x0t]] is a 3 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=8X0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8X0T 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]] 2.5Å</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=8x0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8x0t OCA], [https://pdbe.org/8x0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8x0t RCSB], [https://www.ebi.ac.uk/pdbsum/8x0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8x0t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FZD8_HUMAN FZD8_HUMAN] Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.<ref>PMID:11448771</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Wnt pathway is an evolutionarily conserved pathway involved in stem cell homeostasis and tissue regeneration. Aberrant signaling in the Wnt pathway is highly associated with cancer. Developing antibodies to block overactivation of Frizzled receptors (FZDs), the main receptors in the Wnt pathway, is one of the viable options for treating cancer. However, obtaining isoform-specific antibodies is often challenging due to the high degree of homology among the ten FZDs. In this study, by using a synthetic library, we identified an antibody named pF8_AC3 that preferentially binds to FZD8. Guided by the structure of the complex of pF8_AC3 and FZD8, a second-generation targeted library was further constructed, and finally, the FZD8-specific antibody sF8_AG6 was obtained. Cell-based assays showed that these antibodies could selectively block FZD8-mediated signaling activation. Taken together, these antibodies have the potential to be developed into therapeutic drugs in the future. | |||
Identification and functional validation of FZD8-specific antibodies.,Li N, Ge Q, Guo Q, Tao Y Int J Biol Macromol. 2023 Nov 3;254(Pt 2):127846. doi: , 10.1016/j.ijbiomac.2023.127846. PMID:37926311<ref>PMID:37926311</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8x0t" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Ge Q]] | |||
[[Category: Li N]] | |||