1fsh

STRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAYSTRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAY

Structural highlights

1fsh 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.

Publication Abstract from PubMed

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.

Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.,Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J Nat Struct Biol. 2000 Dec;7(12):1178-84. PMID:11101902^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

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OCA

[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

[5] 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

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1fsh

STRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAYSTRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAY

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

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1fsh

STRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAYSTRUCTURAL BASIS OF THE RECOGNITION OF THE DISHEVELLED DEP DOMAIN IN THE WNT SIGNALING PATHWAY

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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