Title : Structural analysis of the synaptic protein
neuroligin and its beta-
neurexin complex:
determinants for folding and cell adhesion
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 beta- 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 alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism