​The structure of Dscam, a neural receptor that mediates self-avoidance

​We have solved the structure of a headpiece of a fascinating receptor molecule Dscam (Down Syndrome Cell Adhesion Molecule) from Drosophila. Dscam has unprecedented 38,000 isoforms generated by alternative splicing from a single gene. Each neuron expresses a small set of isoforms as its surface marker. The homophilic binding of these isoforms between sister branches from the same neuron will result in self-avoidance, a mechanism to ensure that the neurites from the same neuron should not connect, a necessary process to establish the correct neuronal network. Our structure encompasses the N-terminal four Ig-like domains, of which Ig2 and Ig3 are variable among different isoforms. We demonstrate how its horseshoe like conformation carries out the hemophilic interaction. Our subsequent publication further defines how several selected isoforms use the identical homophilic binding model but with distinct specificity for isoform recognition.