T-cadherin structures reveal a novel adhesive binding mechanism

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Item Type:	Article
Title:	T-cadherin structures reveal a novel adhesive binding mechanism
Creators Name:	Ciatto, C., Bahna, F., Zampieri, N., VanSteenhouse, H.C., Katsamba, P.S., Ahlsen, G., Harrison, O.J., Brasch, J., Jin, X., Posy, S., Vendome, J., Ranscht, B., Jessell, T.M., Honig, B. and Shapiro, L.
Abstract:	Vertebrate genomes encode 19 classical cadherins and about 100 nonclassical cadherins. Adhesion by classical cadherins depends on binding interactions in their N-terminal EC1 domains, which swap N-terminal beta-strands between partner molecules from apposing cells. However, strand-swapping sequence signatures are absent from nonclassical cadherins, raising the question of how these proteins function in adhesion. Here, we show that T-cadherin, a glycosylphosphatidylinositol (GPI)-anchored cadherin, forms dimers through an alternative nonswapped interface near the EC1-EC2 calcium-binding sites. Mutations within this interface ablate the adhesive capacity of T-cadherin. These nonadhesive T-cadherin mutants also lose the ability to regulate neurite outgrowth from T-cadherin-expressing neurons. Our findings reveal the likely molecular architecture of the T-cadherin homophilic interface and its requirement for axon outgrowth regulation. The adhesive binding mode used by T-cadherin may also be used by other nonclassical cadherins.
Keywords:	Cadherins, Calcium, Cultured Cells, Mutation, Neurons, Protein Binding, Protein Multimerization, Secondary Protein Structure, X-Ray Crystallography, Animals, Chickens, Mice, Rats
Source:	Nature Structural & Molecular Biology
ISSN:	1545-9993
Publisher:	Nature Publishing Group
Volume:	17
Number:	3
Page Range:	339-347
Date:	March 2010
Official Publication:	https://doi.org/10.1038/nsmb.1781
PubMed:	View item in PubMed

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