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

Journal article

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.

Authors: Seiradake, E; Coles, C; Perestenko, P; Harlos, K; McIlhinney, R

• Publication status: Published
• Journal: EMBO journal
• Volume: 30
• Issue: 21
• Pages: 4479-4488
• Publication date: 2011-11-01
• DOI: 10.1038/emboj.2011.346
• EISSN: 1460-2075
• ISSN: 0261-4189
• Language: English
• Keywords: Protein Binding; Protein Conformation; Receptors, Cell Surface; Models, Biological; Humans; Tissue Distribution; HEK293 Cells; Membrane Glycoproteins; Ligands; Synapses; GPI-Linked Proteins; Models, Molecular; Nerve Tissue Proteins; Transfection