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EMBO J. 2011 Sep 23;30(21):4479-88. doi: 10.1038/emboj.2011.346.

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

Author information

1
Division of Structural Biology, CR-UK Receptor Structure Research Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Abstract

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.

PMID:
21946559
PMCID:
PMC3230378
DOI:
10.1038/emboj.2011.346
[Indexed for MEDLINE]
Free PMC Article

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