Structures of Neuroligin-1 And the Neuroligin-1/Neurexin-1beta Complex Reveal Specific Protein-Protein And Protein-Ca**2+ Interactions

Journal Article · Thu May 28 04:00:00 EDT 2009 · Neuron 56:992,2007

OSTI ID:953536

Arac, D; Boucard, A A; Ozkan, E A; Strop, P; Newell, E; Sudhof, T C; Brunger, A T

Neurexins and neuroligins provide trans-synaptic connectivity by the Ca{sup 2+}-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 Ca{sup 2+}. 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.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 953536
• Report Number(s): SLAC-REPRINT-2009-347
• Journal Information: Neuron 56:992,2007, Journal Name: Neuron 56:992,2007 Journal Issue: 6 Vol. 56; ISSN 0896-6273; ISSN NERNET
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
AFFINITY
CRYSTAL STRUCTURE
DIMERS
INTERACTIONS
INTERFACES
MONOMERS
MUTATIONS
Other
OTHER
PROTEINS
SURFACES