Regulation of Neurexin 1[beta] Tertiary Structure and Ligand Binding through Alternative Splicing

Journal Article · Mon Aug 04 04:00:00 EDT 2008 · Structure

DOI:https://doi.org/10.1016/j.str.2008.01.005· OSTI ID:1006590

Shen, Kaiser C; Kuczynska, Dorota A; Wu, Irene J; Murray, Beverly H; Sheckler, Lauren R; Rudenko, Gabby ^[1]

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1. Michigan

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 1{beta} carrying an alternative splice insert at site SS{number_sign}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 1{beta}+SS{number_sign}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 {beta}10-{beta}11 into a helix rearranging the binding site for neuroligins, and rearranges the Ca{sup 2+}-binding site required for ligand binding, increasing its affinity. Our structures reveal the mechanism by which neurexin 1{beta} isoforms acquire neuroligin splice isoform selectivity.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006590
• Journal Information: Structure, Journal Name: Structure Journal Issue: 03, 2008 Vol. 16
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
AFFINITY
CONVERSION
EXCITATION
IN VITRO
INHIBITION
INTERACTIONS
LIGANDS
MEMBRANE PROTEINS
MENTAL DISORDERS
NERVE CELLS
SPLICING