title: 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.
authors: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors: H C
authors: HC
authors: Wong
authors: J
authors: J
authors: Mao
authors: J T
authors: JT
authors: Nguyen
authors: S
authors: S
authors: Srinivas
authors: W
authors: W
authors: Zhang
authors: B
authors: B
authors: Liu
authors: L
authors: L
authors: Li
authors: D
authors: D
authors: Wu
authors: J
authors: J
authors: Zheng
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D051153:Wnt Proteins; D029961:Zebrafish Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins