First Author | Seiradake E | Year | 2011 |
Journal | EMBO J | Volume | 30 |
Issue | 21 | Pages | 4479-88 |
PubMed ID | 21946559 | Mgi Jnum | J:180007 |
Mgi Id | MGI:5304985 | Doi | 10.1038/emboj.2011.346 |
Citation | Seiradake E, et al. (2011) Structural basis for cell surface patterning through NetrinG-NGL interactions. EMBO J 30(21):4479-88 |
abstractText | Brain wiring depends on cells making highly localized and selective connections through surface protein-protein interactions, including those between NetrinGs and NetrinG ligands (NGLs). The NetrinGs are members of the structurally uncharacterized netrin family. We present a comprehensive crystallographic analysis comprising NetrinG1-NGL1 and NetrinG2-NGL2 complexes, unliganded NetrinG2 and NGL3. Cognate NetrinG-NGL interactions depend on three specificity-conferring NetrinG loops, clasped tightly by matching NGL surfaces. We engineered these NGL surfaces to implant custom-made affinities for NetrinG1 and NetrinG2. In a cellular patterning assay, we demonstrate that NetrinG-binding selectivity can direct the sorting of a mixed population of NGLs into discrete cell surface subdomains. These results provide a molecular model for selectivity-based patterning in a neuronal recognition system, dysregulation of which is associated with severe neuropsychological disorders. |