T-cadherin structures reveal a novel adhesive binding mechanism

Item Type:	Article
Title:	T-cadherin structures reveal a novel adhesive binding mechanism
Creators Name:	Ciatto, C. and Bahna, F. and Zampieri, N. and VanSteenhouse, H.C. and Katsamba, P.S. and Ahlsen, G. and Harrison, O.J. and Brasch, J. and Jin, X. and Posy, S. and Vendome, J. and Ranscht, B. and Jessell, T.M. and 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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