| First Author | Ranaivoson FM | Year | 2015 |
| Journal | Structure | Volume | 23 |
| Issue | 9 | Pages | 1665-77 |
| PubMed ID | 26235031 | Mgi Jnum | J:225579 |
| Mgi Id | MGI:5693672 | Doi | 10.1016/j.str.2015.06.022 |
| Citation | Ranaivoson FM, et al. (2015) Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development. Structure 23(9):1665-77 |
| abstractText | Latrophilins (LPHNs) are adhesion-like G-protein-coupled receptors implicated in attention-deficit/hyperactivity disorder. Recently, LPHN3 was found to regulate excitatory synapse number through trans interactions with fibronectin leucine-rich repeat transmembrane 3 (FLRT3). By isothermal titration calorimetry, we determined that only the olfactomedin (OLF) domain of LPHN3 is necessary for FLRT3 association. By multi-crystal native single-wavelength anomalous diffraction phasing, we determined the crystal structure of the OLF domain. This structure is a five-bladed beta propeller with a Ca(2+) ion bound in the central pore, which is capped by a mobile loop that allows the ion to exchange with the solvent. The crystal structure of the OLF/FLRT3 complex shows that LPHN3-OLF in the closed state binds with high affinity to the concave face of FLRT3-LRR with a combination of hydrophobic and charged residues. Our study provides structural and functional insights into the molecular mechanism underlying the contribution of LPHN3/FLRT3 to the development of glutamatergic synapses. |
