Interaction between the internal motif KTXXXI of Idax and mDvl PDZ domain.
Dishevelled (Dvl) is the essential signal transduction component of both canonical and non-canonical Wnt signaling pathways. The cysteine-rich protein Idax acts as a negative regulator of Wnt signaling in mammals by interaction with Dvl in the region of the PDZ domain. In an effort to clarify the structural basis of this interaction, we used nuclear magnetic resonance spectroscopy to study the interaction of the Dvl PDZ domain with Idax. We first confirmed that the C-terminal region of Idax consisting of residues 109-198 binds to the PDZ domain of mouse Dvl-1 at the conventional C-terminal peptide-binding groove. However, instead of the C-terminus of Idax, we showed that a peptide of an internal sequence of Idax containing a KTXXXI motif is important in the interaction with a binding affinity estimated at 56 microM. Such internal motif identified in this study suggests a new type of sequence motif recognition for Dvl PDZ domain.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Timothy B C
TB
London
Ho-Jin
HJ
Lee
Youming
Y
Shao
Jie
J
Zheng
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003198:Computer Simulation; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; C418221:CXXC4 protein, human; D002352:Carrier Proteins; C485963:Cxxc4 protein, rat; D004268:DNA-Binding Proteins; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C000606580:Dvl1 protein, rat; D010750:Phosphoproteins; D011506:Proteins; D014157:Transcription Factors