Structural basis for cell surface patterning through NetrinG-NGL interactions

Elena Seiradake, Charlotte H Coles, Pavel V Perestenko, Karl Harlos, Robert A J McIlhinney, Alexandru Radu Aricescu, E. Yvonne Jones

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)4479-88
Number of pages10
JournalEMBO Journal
Issue number21
Publication statusPublished - 23 Sep 2011


  • Brain patterning
  • Crystal structure
  • Protein Engineering
  • Schizophrenia
  • Synaptic adhesion


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