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Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions.

Neuron | Dec 20, 2007

http://www.ncbi.nlm.nih.gov/pubmed/18093522

Neurexins and neuroligins provide trans-synaptic connectivity by the Ca2+-dependent interaction of their alternatively spliced extracellular domains. Neuroligins specify synapses in an activity-dependent manner, presumably by binding to neurexins. Here, we present the crystal structures of neuroligin-1 in isolation and in complex with neurexin-1 beta. Neuroligin-1 forms a constitutive dimer, and two neurexin-1 beta monomers bind to two identical surfaces on the opposite faces of the neuroligin-1 dimer to form a heterotetramer. The neuroligin-1/neurexin-1 beta complex exhibits a nanomolar affinity and includes a large binding interface that contains bound Ca2+. Alternatively spliced sites in neurexin-1 beta and in neuroligin-1 are positioned nearby the binding interface, explaining how they regulate the interaction. Structure-based mutations of neuroligin-1 at the interface disrupt binding to neurexin-1 beta, but not the folding of neuroligin-1 and confirm the validity of the binding interface of the neuroligin-1/neurexin-1 beta complex. Our results provide molecular insights for understanding the role of cell-adhesion proteins in synapse function.

Pubmed ID: 18093522 RIS Download

Mesh terms: Alternative Splicing | Amino Acid Sequence | Animals | Calcium | Cell Adhesion Molecules, Neuronal | Cells, Cultured | Crystallography | Membrane Proteins | Models, Biological | Models, Molecular | Molecular Sequence Data | Nerve Tissue Proteins | Protein Binding | Protein Conformation | Protein Folding | Rats | Recombinant Proteins | Spectrum Analysis | Surface Plasmon Resonance | Synapses

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Associated grants

  • Agency: NIMH NIH HHS, Id: R37 MH52804-08

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