The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

Meier, M.; Gupta, M.; Akgül, S.; McDougall, M.; Imhof, T.; Nikodemus, D.; Reuten, R.; Moya-Torres, A.; To, V.; Ferens, F.; Heide, F.; Padilla-Meier, G.P.; Kukura, P.; Huang, W.; Gerisch, B.; Mörgelin, M.; Poole, K.; Antebi, A.; Koch, M.; Stetefeld, J.

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

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Item Type:	Article
Title:	The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
Creators Name:	Meier, M., Gupta, M., Akgül, S., McDougall, M., Imhof, T., Nikodemus, D., Reuten, R., Moya-Torres, A., To, V., Ferens, F., Heide, F., Padilla-Meier, G.P., Kukura, P., Huang, W., Gerisch, B., Mörgelin, M., Poole, K., Antebi, A., Koch, M. and Stetefeld, J.
Abstract:	Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.
Keywords:	Biophysical Chemistry, Caenorhabditis Elegans, Intracellular Signalling Peptides and Proteins, X-Ray Crystallography
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	14
Number:	1
Page Range:	1226
Date:	3 March 2023
Official Publication:	https://doi.org/10.1038/s41467-023-36692-w
PubMed:	View item in PubMed

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