Structural basis for cell surface patterning through NetrinG-NGL interactions.
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.
Mesh Terms:
GPI-Linked Proteins, HEK293 Cells, Humans, Ligands, Membrane Glycoproteins, Models, Biological, Models, Molecular, Nerve Tissue Proteins, Netrins, Protein Binding, Protein Conformation, Receptors, Cell Surface, Synapses, Tissue Distribution, Transfection
GPI-Linked Proteins, HEK293 Cells, Humans, Ligands, Membrane Glycoproteins, Models, Biological, Models, Molecular, Nerve Tissue Proteins, Netrins, Protein Binding, Protein Conformation, Receptors, Cell Surface, Synapses, Tissue Distribution, Transfection
EMBO J
Date: Sep. 23, 2011
PubMed ID: 21946559
View in: Pubmed Google Scholar
Download Curated Data For This Publication
226613
Switch View:
- Interactions 2