Title : Structural Basis of Diverse Homophilic Recognition by Clustered α- and β-
Protocadherins
Abstract :
- Clustered proto cadherin proteins (α-, β-, and γ-Pcdhs) provide a high level of cell-surface diversity to individual vertebrate neurons, engaging in highly specific homophilic interactions to mediate important roles in mammalian neural circuit development
- How Pcdhs bind homophilically through their extracellular cadherin ( EC ) domains among dozens of highly similar isoforms has not been determined
- Here, we report crystal structures for extracellular regions from four mouse Pcdh isoforms (α 4, α7, β6, and β8 ), revealing a canonical head-to-tail interaction mode for homophilic trans dimers comprising primary intermolecular EC1 :EC4 and EC2 :EC3 interactions
- A subset of trans interface residues exhibit isoform-specific conservation, suggesting roles in recognition specificity
- Mutation of these residues, along with trans-interacting partner residues , altered the specificities of Pcdh interactions
- Together, these data show how sequence variation among Pcdh isoforms encodes their diverse strict homophilic recognition specificities, which are required for their key roles in neural circuit assembly