Structural Analysis of the Synaptic Protein Neuroligin and Its β-Neurexin Complex: Determinants for Folding and Cell Adhesion

Igor P. Fabrichny, Philippe Leone, Gerlind Sulzenbacher, Davide Comoletti, Meghan T. Miller, Palmer Taylor, Yves Bourne, Pascale Marchot

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

The neuroligins are postsynaptic cell adhesion proteins whose associations with presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin and neurexin genes appear to be associated with autism and mental retardation. The crystal structure of a neuroligin reveals features not found in its catalytically active relatives, such as the fully hydrophobic interface forming the functional neuroligin dimer; the conformations of surface loops surrounding the vestigial active center; the location of determinants that are critical for folding and processing; and the absence of a macromolecular dipole and presence of an electronegative, hydrophilic surface for neurexin binding. The structure of a β-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin and, despite a limited resolution, provides substantial information on the Ca2+-dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how an α/β-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalNeuron
Volume56
Issue number6
DOIs
StatePublished - Dec 20 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • CELLBIO
  • MOLNEURO

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    Fabrichny, I. P., Leone, P., Sulzenbacher, G., Comoletti, D., Miller, M. T., Taylor, P., Bourne, Y., & Marchot, P. (2007). Structural Analysis of the Synaptic Protein Neuroligin and Its β-Neurexin Complex: Determinants for Folding and Cell Adhesion. Neuron, 56(6), 979-991. https://doi.org/10.1016/j.neuron.2007.11.013