8j9n

From Proteopedia

(Difference between revisions)

Revision as of 10:06, 17 January 2024

Gq bound FZD1 in ligand-free state

Structural highlights

8j9n is a 5 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FZD1_HUMAN Receptor for Wnt proteins (PubMed:10557084). Activated by WNT3A, WNT3, WNT1 and to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6, WNT7A or WNT7B (PubMed:10557084). Contradictory results showing activation by WNT7B have been described for mouse (By similarity). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:10557084). The canonical Wnt/beta-catenin 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 (PubMed:10557084). 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 (Probable).[UniProtKB:O70421]^[1] (Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium.^[2]

Publication Abstract from PubMed

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways.,Zhang Z, Lin X, Wei L, Wu Y, Xu L, Wu L, Wei X, Zhao S, Zhu X, Xu F Cell Discov. 2024 Jan 5;10(1):3. doi: 10.1038/s41421-023-00627-y. PMID:38182578^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gazit A, Yaniv A, Bafico A, Pramila T, Igarashi M, Kitajewski J, Aaronson SA. Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response. Oncogene. 1999 Oct 28;18(44):5959-66. PMID:10557084 doi:10.1038/sj.onc.1202985
↑ Tao L, Zhang J, Meraner P, Tovaglieri A, Wu X, Gerhard R, Zhang X, Stallcup WB, Miao J, He X, Hurdle JG, Breault DT, Brass AL, Dong M. Frizzled proteins are colonic epithelial receptors for C. difficile toxin B. Nature. 2016 Oct 20;538(7625):350-355. doi: 10.1038/nature19799. Epub 2016 Sep, 28. PMID:27680706 doi:http://dx.doi.org/10.1038/nature19799
↑ Zhang Z, Lin X, Wei L, Wu Y, Xu L, Wu L, Wei X, Zhao S, Zhu X, Xu F. A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways. Cell Discov. 2024 Jan 5;10(1):3. PMID:38182578 doi:10.1038/s41421-023-00627-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8j9n"

Categories: Homo sapiens | Large Structures | Vicugna pacos | Lin X | Xu F

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8j9n is ON HOLD
+==Gq bound FZD1 in ligand-free state==
+<StructureSection load='8j9n' size='340' side='right'caption='[[8j9n]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8j9n]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8J9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J9N FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#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=8j9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j9n OCA], [https://pdbe.org/8j9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j9n RCSB], [https://www.ebi.ac.uk/pdbsum/8j9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j9n ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FZD1_HUMAN FZD1_HUMAN] Receptor for Wnt proteins (PubMed:10557084). Activated by WNT3A, WNT3, WNT1 and to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6, WNT7A or WNT7B (PubMed:10557084). Contradictory results showing activation by WNT7B have been described for mouse (By similarity). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:10557084). The canonical Wnt/beta-catenin 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 (PubMed:10557084). 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 (Probable).[UniProtKB:O70421]<ref>PMID:10557084</ref>   (Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium.<ref>PMID:27680706</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.
-Authors: Lin, X., Xu, F.
+A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways.,Zhang Z, Lin X, Wei L, Wu Y, Xu L, Wu L, Wei X, Zhao S, Zhu X, Xu F Cell Discov. 2024 Jan 5;10(1):3. doi: 10.1038/s41421-023-00627-y. PMID:38182578<ref>PMID:38182578</ref>
-Description: Gq bound FZD1 in ligand-free state
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Xu, F]]
+<div class="pdbe-citations 8j9n" style="background-color:#fffaf0;"></div>
-[[Category: Lin, X]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Vicugna pacos]]
+[[Category: Lin X]]
+[[Category: Xu F]]

8j9n

From Proteopedia

Revision as of 10:06, 17 January 2024

Gq bound FZD1 in ligand-free state

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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