3ML6

a complex between Dishevelled2 and clathrin adaptor AP-2

Summary for 3ML6

• Entry DOI: 10.2210/pdb3ml6/pdb
• Descriptor: Chimeric complex between protein Dishevelled2 homolog dvl-2 and clathrin adaptor AP-2 complex subunit mu (1 entity in total)
• Functional Keywords: dishevelled, ap2, frizzled internalization, non-canonical wnt signaling, protein transport
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 260420.20

Authors

Yu, A.,Xing, Y.,Harrison, S.C.,Kirchhausen, T.L. (deposition date: 2010-04-16, release date: 2010-08-11, Last modification date: 2023-09-06)

Primary citation

Yu, A.,Xing, Y.,Harrison, S.C.,Kirchhausen, T.
Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling.
Structure, 18:1311-1320, 2010

PubMed Abstract: Wnt association with its receptor, Frizzled (Fz), and recruitment by the latter of an adaptor, Dishevelled (Dvl), initiates signaling through at least two distinct pathways ("canonical" and "noncanonical"). Endocytosis and compartmentalization help determine the signaling outcome. Our previous work has shown that Dvl2 links at least one Frizzled family member (Fz4) to clathrin-mediated endocytosis by interacting with the μ2 subunit of the AP-2 clathrin adaptor, through both a classical endocytic tyrosine motif and a so-called "DEP domain." We report here the crystal structure of a chimeric protein that mimics the Dvl2-μ2 complex. The DEP domain binds at one end of the elongated, C-terminal domain of μ2. This domain:domain interface shows that parts of the μ2 surface distinct from the tyrosine-motif site can help recruit specific receptors or adaptors into a clathrin coated pit. Mutation of residues at the DEP-μ2 contact or in the tyrosine motif reduce affinity of Dvl2 for μ2 and block efficient internalization of Fz4 in response to ligation by Wnt5a. The crystal structure has thus allowed us to identify the specific interaction that leads to Frizzled uptake and to downstream, noncanonical signaling events.

PubMed: 20947020
DOI: 10.1016/j.str.2010.07.010

Experimental method

X-RAY DIFFRACTION (3.5 Å)