6o3e | pdb_00006o3e
mouse aE-catenin 82-883
Structural highlights
Function[CTNA1_MOUSE] Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. May play a crucial role in cell differentiation.[1] Publication Abstract from PubMedAdherens Junctions (AJs) are cell-cell adhesion complexes that sense and propagate mechanical forces by coupling cadherins to the actin cytoskeleton via beta-catenin and the F-actin binding protein alphaE-catenin. When subjected to mechanical force, the cadherin*catenin complex can tightly link to F-actin through alphaE-catenin, and also recruits the F-actin-binding protein vinculin. In this study, labeling of native cysteines combined with mass spectrometry revealed conformational changes in alphaE-catenin upon binding to the E-cadherin*beta-catenin complex, vinculin and F-actin. A method to apply physiologically meaningful forces in solution revealed force-induced conformational changes in alphaE-catenin when bound to F-actin. Comparisons of wild-type alphaE-catenin and a mutant with enhanced vinculin affinity using cysteine labeling and isothermal titration calorimetry provide evidence for allosteric coupling of the N-terminal beta-catenin-binding and the middle (M) vinculin-binding domain of alphaE-catenin. Cysteine labeling also revealed possible crosstalk between the actin-binding domain and the rest of the protein. The data provide insight into how binding partners and mechanical stress can regulate the conformation of full-length alphaE-catenin, and identify the M domain as a key transmitter of conformational changes. Binding partner- and force-promoted changes in alphaE-catenin conformation probed by native cysteine labeling.,Terekhova K, Pokutta S, Kee YS, Li J, Tajkhorshid E, Fuller G, Dunn AR, Weis WI Sci Rep. 2019 Oct 25;9(1):15375. doi: 10.1038/s41598-019-51816-3. PMID:31653927[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
