7ler | pdb_00007ler
Netrin-1 filament assembly
Structural highlights
FunctionNET1_CHICK Netrins control guidance of CNS commissural axons and peripheral motor axons. Promotes neurite outgrowth from commissural axons but acts as a chemorepellent for trochlear motor axons. These effects are mediated by distinct receptors. Publication Abstract from PubMedNetrin-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. The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation.,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 GP, Kukura P, Huang W, Gerisch B, Morgelin M, Poole K, Antebi A, Koch M, Stetefeld J Nat Commun. 2023 Mar 3;14(1):1226. doi: 10.1038/s41467-023-36692-w. PMID:36869049[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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