Molecular recognition mechanisms during neuronal synapse formation are still incompletely understood. The neuronal transmembrane protein family of Teneurins is required for synaptic partner matching in the visual and hippocampal systems in vertebrates. It remains however unclear how individual Teneurin molecules form macromolecular cis- and trans-cellular protein complexes at the neuronal synapse. Here, I present a <3 A cryo-EM structure of the dimeric ectodomain of human Teneurin4. The structure reveals a compact conformation of the dimer that is stabilized by C-rich, YD-shell and ABO-mediated interactions. We identified three conserved calcium binding sites in the C-richemical domain that control the compactness and stability of Teneurin4 dimers. We then use in vivo cellular assays to visualize how these compact cis dimers establish homomeric trans interactions. Together, these findings support a role for Teneurins as a scaffold for macromolecular complex assembly and the establishment of cis- and !rans-synaptic interactions to construct functional neuronal circuits
About the speaker
Asslstant Professor and Group Leader of the Molecular and Cellular Neurobiology Laboratory at TU Delft. She carried out her PhD research in the Neurobiology Department of the Harvard Medical School and the Cancer Biology Department of the Dana Farber Cancer Center, Boston, USA
