8os6

Structure of a GFRA1/GDNF LICAM complex

spinqualitylabelsall models 8os6, resolution 2.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8os6 is a 20 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.66Å Ligands: FUC, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q98TT9_DANRE Publication Abstract from PubMed Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRalpha1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRalpha1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRalpha1 assembly determined by crystallography and electron microscopy, revealing two GFRalpha1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRalpha1:GFRalpha1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRalpha1. Architecture and regulation of a GDNF-GFRalpha1 synaptic adhesion assembly.,Houghton FM, Adams SE, Rios AS, Masino L, Purkiss AG, Briggs DC, Ledda F, McDonald NQ Nat Commun. 2023 Nov 20;14(1):7551. doi: 10.1038/s41467-023-43148-8. PMID:37985758 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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