PDBsum entry: 1fsh

Signaling protein

PDB id: 1fsh

Contents

Protein chain

94 a.a. *

* Residue conservation analysis

PDB id:

1fsh

Name:

Signaling protein

Title:

Structural basis of the recognition of the dishevelled dep domain in the wnt signaling pathway

Structure:

Dishevelled-1. Chain: a. Fragment: dep domain (residues 391-495). Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

H.C.Wong,J.Zheng

Key ref:

H.C.Wong et al. (2000). Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway. Nat Struct Biol, 7, 1178-1184. PubMed id: 11101902 DOI: 10.1038/82047

Date:

08-Sep-00 Release date: 08-Mar-01

Protein chain

P51141  (DVL1_MOUSE) -  Segment polarity protein dishevelled homolog DVL-1

Seq: 695 a.a.

Struc: 94 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: multicellular organismal development (1 term)
• Biochemical function: signal transducer activity (1 term)

DOI no: 10.1038/82047

Nat Struct Biol 7:1178-1184 (2000)

PubMed id: 11101902

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

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

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.

Selected figure(s)

Figure 3.
Figure 3. Solution structure of the DEP domain of mDvl1. a, Stereo view of the peptide backbone (N, C , C') of 20 superimposed structures of the DEP domain (residues 402 -495). -strands are yellow, and -helices are magenta. b, Ribbon diagram of the DEP structure with the lowest target function. The images in (a) were generated using MOLMOL48, and that in (b) was generated using MOLSCRIPT49 and render50.

Figure 5.
Figure 5. Surface potential of the DEP domain. a, A cluster of basic residues that indicates a putative membrane binding site shown. b, Front view of the image that has been rotated 90° with respect to (a). The circled area shows the electrostatic dipole formed by Lys 434, Asp 445 and Asp 448. The images were produced using the program GRASP51. In the surface map, red regions represent negative potential, blue positive and white neutral.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 1178-1184) copyright 2000.

Figures were selected by the author.