The structure of the ligand-binding domain of neurexin I beta: Regulation of LNS domain function by alternative splicing

Neurexins are expressed in hundreds of isoforms on the neuronal cell surfac e, where they may function as cell recognition molecules. Neurexins contain LNS domains, folding units found in many proteins like the G domain of lam inin A, agrin, and slit. The crystal structure of neurexin I beta, a single LNS domain, reveals two seven-stranded beta sheets forming a jelly roll fo ld with unexpected structural similarity Po lectins. The LNS domains of neu rexin and agrin undergo alternative splicing that modulates their affinity for protein ligands in a neuron-specific manner. These splice sites are loc alized within loops at one edge of the jelly roll, suggesting a distinct pr otein interaction surface in LNS domains that is regulated by alternative s plicing.