We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
T-cadherin structures reveal a novel adhesive binding mechanism.
- Authors
Ciatto, Carlo; Bahna, Fabiana; Zampieri, Niccolò; VanSteenhouse, Harper C.; Katsamba, Phini S.; Ahlsen, Goran; Harrison, Oliver J.; Brasch, Julia; Xiangshu Jin; Posy, Shoshana; Vendome, Jeremie; Ranscht, Barbara; Jessell, Thomas M; Honig, Barry; Shapiro, Lawrence
- 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 β-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.
- Subjects
CADHERINS; GENOMES; VERTEBRATES; AXONS; NEURONS
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 3, p339
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1781