Structure of Synaptic Protein May Provide Clues to Autism

Mutations in genes encoding neuroligins are associated with autism and mental retardation

THURSDAY, Dec. 27 (HealthDay News) -- A new study provides insight into the molecular structure of neuroligins, a family of postsynaptic cell adhesion proteins required for neural synapse formation. These findings are relevant to the study of autism because mutations in the genes encoding neuroligins have been implicated in autism spectrum disorders and mental retardation. The research is published in the December issue of Neuron.

Igor P. Fabrichny, of the Universite de la Mediterranee in Marseille, France, and colleagues analyzed the molecular structure of the synaptic protein neuroligin and the β-neurexin-neuroligin complex.

The researchers describe the molecular structure of neuroligins, including a hydrophobic interface comprising the neuroligin dimer, the pattern of surface loops surrounding the vestigial active center, the critical features for molecular folding and processing, and a hydrophilic surface for neurexin binding.

"The structure of a β-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin, and despite its limited resolution, provides substantial information on the Ca2+-dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how a 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," the authors conclude.

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