4R10

A conserved phosphorylation switch controls the interaction between cadherin and beta-catenin in vitro and in vivo

Summary for 4R10

• Entry DOI: 10.2210/pdb4r10/pdb
• Related: 4R0Z 4R11
• Descriptor: Protein humpback-2, Cadherin-related hmr-1, SULFATE ION, ... (5 entities in total)
• Functional Keywords: armadillo repeat, cell adhesion, phosphorylation, cell adhesion-protein binding complex, cell adhesion/protein binding
• Biological source: Caenorhabditis elegans (roundworm); More
• Cellular location: Cell junction, adherens junction : O44326; Cell membrane ; Single-pass type I membrane protein : Q967F4
• Total number of polymer chains: 2
• Total formula weight: 71971.76

Authors

Choi, H.-J.,Loveless, T.,Lynch, A.,Bang, I.,Hardin, J.,Weis, W.I. (deposition date: 2014-08-03, release date: 2015-04-29, Last modification date: 2024-10-16)

Primary citation

Choi, H.J.,Loveless, T.,Lynch, A.M.,Bang, I.,Hardin, J.,Weis, W.I.
A Conserved Phosphorylation Switch Controls the Interaction between Cadherin and beta-Catenin In Vitro and In Vivo
Dev.Cell, 33:82-93, 2015

PubMed Abstract: In metazoan adherens junctions, β-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein α-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for β-catenin and promotes cell-cell adhesion in cell culture systems, but its importance has not been demonstrated in vivo. Here, we identify a critical phosphorylated serine in the C. elegans cadherin HMR-1 required for strong binding to the β-catenin homolog HMP-2. Ablation of this phosphoserine interaction produces developmental defects that resemble full loss-of-function (Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for β-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous β-catenins; for example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1 mediates transcriptional activation through interactions with POP-1/Tcf. Our structural data define critical sequence differences responsible for the unique ligand specificities of these two proteins.

PubMed: 25850673
DOI: 10.1016/j.devcel.2015.02.005

Experimental method

X-RAY DIFFRACTION (2.3 Å)