4ons
From Proteopedia
Structural and thermodynamic characterization of cadherin-beta-catenin-alpha-catenin complex formation
Structural highlights
Function[CTNA2_MOUSE] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.[1] [2] [3] [CTNB1_MOUSE] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity). Publication Abstract from PubMedThe classical cadherin-beta-catenin-alpha-catenin complex mediates homophilic cell-cell adhesion and mechanically couples the actin cytoskeletons of adjacent cells. Although alpha-catenin binds to beta-catenin and to F-actin, beta-catenin significantly weakens the affinity of alpha-catenin for F-actin. Moreover, alpha-catenin self-associates into homodimers that block beta-catenin binding. We investigated quantitatively and structurally alphaE- and alphaN-catenin dimer formation, their interaction with beta-catenin and the cadherin-beta-catenin complex, and the effect of the alpha-catenin actin-binding domain on beta-catenin association. The two alpha-catenin variants differ in their self-association properties: at physiological temperatures alphaE-catenin homodimerizes 10x more weakly than does alphaN-catenin, but is kinetically trapped in its oligomeric state. Both alphaE- and alphaN-catenin bind to beta-catenin with a Kd of 20 nM, and this affinity is increased by an order of magnitude when cadherin is bound to beta-catenin. We describe the crystal structure of a complex representing the full beta-catenin-alphaN-catenin interface. A three-dimensional model of the cadherin-beta-catenin-alpha-catenin complex based on these new structural data suggests mechanisms for the enhanced stability of the ternary complex. The C-terminal actin-binding domain of alpha-catenin has no influence on the interactions with beta-catenin, arguing against models in which beta-catenin weakens actin binding by stabilizing inhibitory intramolecular interactions between the actin-binding domain and the rest of alpha-catenin. Structural and Thermodynamic Characterization of Cadherin-beta-catenin-alpha-catenin Complex Formation.,Pokutta S, Choi HJ, Ahlsen G, Hansen SD, Weis WI J Biol Chem. 2014 Apr 1. PMID:24692547[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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