1MC7

Solution Structure of mDvl1 PDZ domain

Summary for 1MC7

• Entry DOI: 10.2210/pdb1mc7/pdb
• Descriptor: Segment polarity protein dishevelled homolog DVL-1 (1 entity in total)
• Functional Keywords: pdz domain, wnt signaling, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: P51141
• Total number of polymer chains: 1
• Total formula weight: 10204.45

Authors

Wong, H.-C.,Bourdelas, A.,Shao, Y.,Wu, D.,Shi, D.L.,Zheng, J. (deposition date: 2002-08-05, release date: 2003-09-23, Last modification date: 2024-05-22)

Primary citation

Wong, H.-C.,Bourdelas, A.,Krauss, A.,Lee, H.-J.,Shao, Y.,Wu, D.,Mlodzik, M.,Shi, D.-L.,Zheng, J.
Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled
Mol.Cell, 12:1251-1260, 2003

PubMed Abstract: 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.

PubMed: 14636582
DOI: 10.1016/S1097-2765(03)00427-1

Experimental method

SOLUTION NMR