Regulation of LNS Domain Function by Alternative Splicing: The Structure of the Ligand-Binding Domain of Neurexin Iβ

cules resembling neuropeptides (Petrenko et al., 1996; Neurexins are expressed in hundreds of isoforms on Missler and Südhof, 1998b). Single LNS domains are the neuronal cell surface, where they may function sufficient for ligand binding. b-neurexin containing a as cell recognition molecules. Neurexins contain LNS sole LNS domain binds a-latrotoxin and neuroligin (Ichtdomains, folding units found in many proteins like the chenko et al., 1995; Sugita et al., 1999). The sixth LNS G domain of laminin A, agrin, and slit. The crystal strucdomain of a-neurexin (which is the counterpart to ture of neurexin Ib, a single LNS domain, reveals two b-neurexin) binds a-latrotoxin but not neuroligin (Sugita seven-stranded b sheets forming a jelly roll fold with et al., 1999), while the second LNS domain of a-neurexin unexpected structural similarity to lectins. The LNS alone is sufficient for binding to neurexophilin (Missler domains of neurexin and agrin undergo alternative and Südhof, 1998b). Binding of neuroligin and a-latrosplicing that modulates their affinity for protein ligands toxin is tightly controlled by alternative splicing at site in a neuron-specific manner. These splice sites are #4, localized in the single LNS domain shared by aand localized within loops at one edge of the jelly roll, b-neurexins. suggesting a distinct protein interaction surface in The ability of b-neurexins to interact with neuroligins LNS domains that is regulated by alternative splicing. results in a clear biological function. b-neurexin is lo-