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Publication : Structural basis for cell surface patterning through NetrinG-NGL interactions.

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.
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