| First Author | Jackson VA | Year | 2015 |
| Journal | Structure | Volume | 23 |
| Issue | 4 | Pages | 774-81 |
| PubMed ID | 25728924 | Mgi Jnum | J:224713 |
| Mgi Id | MGI:5688816 | Doi | 10.1016/j.str.2015.01.013 |
| Citation | Jackson VA, et al. (2015) Structural basis of latrophilin-FLRT interaction. Structure 23(4):774-81 |
| abstractText | Latrophilins, receptors for spider venom alpha-latrotoxin, are adhesion type G-protein-coupled receptors with emerging functions in synapse development. The N-terminal region binds the endogenous cell adhesion molecule FLRT, a major regulator of cortical and synapse development. We present crystallographic data for the mouse Latrophilin3 lectin and olfactomedin-like (Olf) domains, thereby revealing the Olf beta-propeller fold and conserved calcium-binding site. We locate the FLRT-Latrophilin binding surfaces by a combination of sequence conservation analysis, point mutagenesis, and surface plasmon resonance experiments. In stripe assays, we show that wild-type Latrophilin3 and its high-affinity interactor FLRT2, but not the binding-impaired mutants we generated, promote HeLa cell adhesion. In contrast, cortical neurons expressing endogenous FLRTs are repelled by wild-type Latrophilin3 and not by the binding-impaired mutant. Taken together, we present molecular level insights into Latrophilin structure, its FLRT-binding mechanism, and a role for Latrophilin and FLRT that goes beyond a simply adhesive interaction. |
