Fig. 1: The structure of the TEN2/LPHN3 complex.

a Schematic diagram of human TEN2. Extracellular domains are colored gray, dark blue, sky blue, cyan, and palecyan for domains 1–5, respectively; transmembrane region (TM) in brown. Domain numbers and descriptions are indicated above scheme. b Schematic diagram of human LPHN3. Lec and Olf domain are colored orange; Hormone Receptor (HormR), GAIN and TM domains are colored gray. Splice site of TEN2 and LPHN3 are shown as red star and black stars, respectively. The constructs that were used in structure determination were TEN2 −SS and LPHN3 +SS. c Schematic diagram of the interaction network between TEN, LPHN, and FLRT at the synapse. TEN and FLRT are localized on the presynaptic cell membrane, while LPHN is localized on the postsynaptic membrane. TEN2 −SS isoform (empty red star) forms trans-cellular complexes with LPHN3 and induces excitatory postsynaptic specializations when LPHN3 simultaneously binds to FLRT3 (left). In contrast, TEN2 +SS isoform (filled red star) induces inhibitory postsynaptic specializations independent of TEN2/LPHN3 interaction or FLRT3 binding (right). d–f The structure of the TEN2/LPHN3 complex as obtained from single-particle cryo-EM analysis. The Lec domain of LPHN3 binds to the side of the β-barrel of TEN. The alternatively spliced site within the β-propeller domain is distal to the Lec binding site on TEN.