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Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.


ABSTRACT: The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. Lys 434 is located at the tip of the beta-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.

SUBMITTER: Wong HC 

PROVIDER: S-EPMC4381838 | biostudies-literature | 2000 Dec

REPOSITORIES: biostudies-literature

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Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.

Wong H C HC   Mao J J   Nguyen J T JT   Srinivas S S   Zhang W W   Liu B B   Li L L   Wu D D   Zheng J J  

Nature structural biology 20001201 12


The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. L  ...[more]

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