Conformational plasticity in the trans-synaptic Neurexin-Cerebellin-Glutamate receptor adhesion complex

摘要

Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein Cerebellin with presynaptic Neurexin and postsynaptic delta-type Glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat Cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-Neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain. In contrast, we show that the interaction of Cerebellin with isolated GluD2 ectodomain is low affinity, which is not simply an outcome of lost avidity when compared to binding with a tetrameric full-length receptor. Rather, high-affinity capture of Cerebellin by post-synaptic terminals is likely controlled by long-distance regulation within this trans-synaptic complex. Altogether, our results suggest unusual conformational flexibility within all components of the complex.