Structural variability and dynamics in the ectodomain of an ancestral-type classical cadherin revealed by AFM imaging.

Shigetaka Nishiguchi, Hiroki Oda

Journal of cell science 2021 Jul 15

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Type III cadherin represents the ancestral form of classical cadherin in bilaterian metazoans. Drosophila possesses type III and type IVa cadherins, known as DN- and DE-cadherins, respectively. Mature DN- and DE-cadherins have 15 and 7 extracellular cadherin domain (EC) repeats, respectively, with DN-cadherin EC6-EC11 homologous to DE-cadherin EC1-EC6. These EC repeats contain predicted complete or partial Ca2+-free inter-EC linkers that potentially contribute to adhesion. Comparative structure-function studies of DN- and DE-cadherins may help us understand the ancestral and derived states of classical cadherin-mediated adhesion mechanisms. Here, using bead aggregation assays, we found that DN-cadherin EC1-EC11 and DE-cadherin EC1-EC6 exhibit Ca2+-dependent adhesive properties. Using high-speed atomic force microscopy (HS-AFM) imaging in solution, we show that both DN- and DE-cadherin ectodomains share a common morphological framework consisting of a strand-like and a globule-like portion. Furthermore, the DN-cadherin EC repeats are highly variable, flexible in morphology and have at least three bendable sites, one of which is located in EC6-EC11 and can act as a flexible hinge. Our findings provide insights into diversification of classical cadherin-mediated adhesion mechanisms. This article has an associated First Person interview with the first author of the paper. © 2021. Published by The Company of Biologists Ltd.

Citation

Shigetaka Nishiguchi, Hiroki Oda. Structural variability and dynamics in the ectodomain of an ancestral-type classical cadherin revealed by AFM imaging. Journal of cell science. 2021 Jul 15;134(14)