7LRF

Netrin-1 in complex with SOS

Summary for 7LRF

• Entry DOI: 10.2210/pdb7lrf/pdb
• Related PRD ID: PRD_900013
• Descriptor: Netrin-1, CHLORIDE ION, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: self assembly, localization, sulfate binding, signaling protein
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 2
• Total formula weight: 105489.21

Authors

Gupta, M.,McDougall, M.,Torres, A.M.,Stetefeld, J. (deposition date: 2021-02-16, release date: 2022-02-23, Last modification date: 2024-10-16)

Primary citation

Meier, M.,Gupta, M.,Akgul, 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.,Morgelin, 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.
Nat Commun, 14:1226-1226, 2023

PubMed 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.

PubMed: 36869049
DOI: 10.1038/s41467-023-36692-w

Experimental method

X-RAY DIFFRACTION (3.21 Å)