2r1d
From Proteopedia
Crystal structure of rat neurexin 1beta in the Ca2+ containing form
Overview
Neurexins and neuroligins play an essential role in synapse function, and their alterations are linked to autistic spectrum disorder. Interactions between neurexins and neuroligins regulate inhibitory and excitatory synaptogenesis in vitro through a "splice-insert signaling code." In particular, neurexin 1beta carrying an alternative splice insert at site SS#4 interacts with neuroligin 2 (found predominantly at inhibitory synapses) but much less so with other neuroligins (those carrying an insert at site B and prevalent at excitatory synapses). The structure of neurexin 1beta+SS#4 reveals dramatic rearrangements to the "hypervariable surface," the binding site for neuroligins. The splice insert protrudes as a long helix into space, triggers conversion of loop beta10-beta11 into a helix rearranging the binding site for neuroligins, and rearranges the Ca(2+)-binding site required for ligand binding, increasing its affinity. Our structures reveal the mechanism by which neurexin 1beta isoforms acquire neuroligin splice isoform selectivity.
About this Structure
Full crystallographic information is available from OCA.
Reference
Regulation of Neurexin 1beta Tertiary Structure and Ligand Binding through Alternative Splicing., Shen KC, Kuczynska DA, Wu IJ, Murray BH, Sheckler LR, Rudenko G, Structure. 2008 Mar;16(3):422-31. PMID:18334217 Page seeded by OCA on Sun May 4 16:04:43 2008
