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==Solution Structure of mDvl1 PDZ domain==
==Solution Structure of mDvl1 PDZ domain==
<StructureSection load='1mc7' size='340' side='right'caption='[[1mc7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='1mc7' size='340' side='right'caption='[[1mc7]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1mc7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MC7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1mc7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MC7 FirstGlance]. <br>
</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=1mc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mc7 OCA], [https://pdbe.org/1mc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mc7 RCSB], [https://www.ebi.ac.uk/pdbsum/1mc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mc7 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1mc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mc7 OCA], [https://pdbe.org/1mc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mc7 RCSB], [https://www.ebi.ac.uk/pdbsum/1mc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mc7 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/DVL1_MOUSE DVL1_MOUSE]] Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).<ref>PMID:12165471</ref> <ref>PMID:15353129</ref> <ref>PMID:11101902</ref> <ref>PMID:19637179</ref>
[https://www.uniprot.org/uniprot/DVL1_MOUSE DVL1_MOUSE] Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).<ref>PMID:12165471</ref> <ref>PMID:15353129</ref> <ref>PMID:11101902</ref> <ref>PMID:19637179</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mc7 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mc7 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cytoplasmic protein Dishevelled (Dvl) and the associated membrane-bound receptor Frizzled (Fz) are essential in canonical and noncanonical Wnt signaling pathways. However, the molecular mechanisms underlying this signaling are not well understood. By using NMR spectroscopy, we determined that an internal sequence of Fz binds to the conventional peptide binding site in the PDZ domain of Dvl; this type of site typically binds to C-terminal binding motifs. The C-terminal region of the Dvl inhibitor Dapper (Dpr) and Frodo bound to the same site. In Xenopus, Dvl binding peptides of Fz and Dpr/Frodo inhibited canonical Wnt signaling and blocked Wnt-induced secondary axis formation in a dose-dependent manner, but did not block noncanonical Wnt signaling mediated by the DEP domain. Together, our results identify a missing molecular connection within the Wnt pathway. Differences in the binding affinity of the Dvl PDZ domain and its binding partners may be important in regulating signal transduction by Dvl.
Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.,Wong HC, Bourdelas A, Krauss A, Lee HJ, Shao Y, Wu D, Mlodzik M, Shi DL, Zheng J Mol Cell. 2003 Nov;12(5):1251-60. PMID:14636582<ref>PMID:14636582</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1mc7" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Bourdelas, A]]
[[Category: Bourdelas A]]
[[Category: Shao, Y]]
[[Category: Shao Y]]
[[Category: Shi, D L]]
[[Category: Shi DL]]
[[Category: Wong, H C]]
[[Category: Wong H-C]]
[[Category: Wu, D]]
[[Category: Wu D]]
[[Category: Zheng, J]]
[[Category: Zheng J]]
[[Category: Pdz domain]]
[[Category: Signaling protein]]
[[Category: Wnt signaling]]

Revision as of 11:34, 10 April 2024

Solution Structure of mDvl1 PDZ domainSolution Structure of mDvl1 PDZ domain

Structural highlights

1mc7 is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DVL1_MOUSE Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Luo ZG, Wang Q, Zhou JZ, Wang J, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, Mei L. Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. Neuron. 2002 Aug 1;35(3):489-505. PMID:12165471
  2. ↑ Pan WJ, Pang SZ, Huang T, Guo HY, Wu D, Li L. Characterization of function of three domains in dishevelled-1: DEP domain is responsible for membrane translocation of dishevelled-1. Cell Res. 2004 Aug;14(4):324-30. PMID:15353129 doi:10.1038/sj.cr.7290232
  3. ↑ Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J. Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway. Nat Struct Biol. 2000 Dec;7(12):1178-84. PMID:11101902 doi:http://dx.doi.org/10.1038/82047
  4. ↑ Lee HJ, Wang NX, Shi DL, Zheng JJ. Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of the protein Dishevelled. Angew Chem Int Ed Engl. 2009;48(35):6448-52. PMID:19637179 doi:10.1002/anie.200902981
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