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Item Type: | Article |
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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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