5lnp | pdb_00005lnp

Domain-swapped dimer of human Dishevelled2 DEP domain: monoclinic crystal form crystallised from monomeric fraction

spinqualitylabelsall models 5lnp, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lnp is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.99Å Ligands: CSO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DVL2_HUMAN Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes (By similarity). Publication Abstract from PubMed Extracellular signals are often transduced by dynamic signaling complexes ("signalosomes") assembled by oligomerizing hub proteins following their recruitment to signal-activated transmembrane receptors. A paradigm is the Wnt signalosome, which is assembled by Dishevelled via reversible head-to-tail polymerization by its DIX domain. Its activity causes stabilization of beta-catenin, a Wnt effector with pivotal roles in animal development and cancer. How Wnt triggers signalosome assembly is unknown. Here, we use structural analysis, as well as biophysical and cell-based assays, to show that the DEP domain of Dishevelled undergoes a conformational switch, from monomeric to swapped dimer, to trigger DIX-dependent polymerization and signaling to beta-catenin. This occurs in two steps: binding of monomeric DEP to Frizzled followed by DEP domain swapping triggered by its high local concentration upon Wnt-induced recruitment into clathrin-coated pits. DEP domain swapping confers directional bias on signaling, and the dimerization provides cross-linking between Dishevelled polymers, illustrating a key principle underlying signalosome formation. Wnt Signalosome Assembly by DEP Domain Swapping of Dishevelled.,Gammons MV, Renko M, Johnson CM, Rutherford TJ, Bienz M Mol Cell. 2016 Oct 6;64(1):92-104. doi: 10.1016/j.molcel.2016.08.026. Epub 2016, Sep 29. PMID:27692984 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA