Establishment of neural connections is critical for proper brain function, and errors in the process are thought to be associated with autism and other disorders. Howard Hughes Medical Institute investigators Axel Brunger (Stanford University) and Thomas Südhof (University of Texas Southwestern Medical Center), working in part at SSRL, have solved the structure of the proteins that form this connection-neuroligin-1 and neurexin-1b—giving clues to how neurons forge physical connections between one another. The results are published in the December 20, 2007, issue of the journal Neuron.

Nerve impulses are triggered when a presynaptic neuron releases a chemical neurotransmitter into the synapse that is recognized by the postsynaptic neuron. Neurexin and neuroligin, respectively, are presynaptic and postsynaptic connector proteins that extend outside of the cells where they are produced and contact one another to form a physical link across the synapse. Using SSRL Beam Line 11-1 and ALS Beam Line 8.2.2, Brunger and colleagues solved the structure of neuroligin-1 by itself and in complex with neurexin-1b.

These structures suggest a model of the structural organization of these cell-adhesion proteins at the synaptic junction. Understanding the molecular mechanism of these proteins in synapse development is a first step in the development of novel therapeutics directed toward treating and possibly curing autism.

D. Araç, A.A. Boucard, E. Özkan, P. Strop, E. Newell, T.C. Südhof, A.T. Brunger. (2007) Structures of Neuroligin-1 and the Neuroligin-1/Neurexin-1b complex reveal specific protein-protein and protein-Ca²⁺ interactions. Neuron, 56, 992-1003.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/neuroligin_hires.html