8OS6

Structure of a GFRA1/GDNF LICAM complex

Summary for 8OS6

• Entry DOI: 10.2210/pdb8os6/pdb
• Descriptor: GDNF family receptor alpha, Glial cell line-derived neurotrophic factor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: adhesion, synapse, complex, signalling, cell adhesion
• Biological source: Danio rerio (zebrafish); More
• Total number of polymer chains: 20
• Total formula weight: 411870.27

Authors

Houghton, F.M.,Adams, S.E.,Briggs, D.C.,McDonald, N.Q. (deposition date: 2023-04-18, release date: 2023-11-29, Last modification date: 2024-11-20)

Primary citation

Houghton, F.M.,Adams, S.E.,Rios, A.S.,Masino, L.,Purkiss, A.G.,Briggs, D.C.,Ledda, F.,McDonald, N.Q.
Architecture and regulation of a GDNF-GFR alpha 1 synaptic adhesion assembly.
Nat Commun, 14:7551-7551, 2023

PubMed Abstract: Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 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 GFRα1:GFRα1 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 GFRα1.

PubMed: 37985758
DOI: 10.1038/s41467-023-43148-8

Experimental method

X-RAY DIFFRACTION (2.66 Å)