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5MR4

Ligand-receptor complex.

Summary for 5MR4
Entry DOI10.2210/pdb5mr4/pdb
Related5MR4 5MR5 5NMZ
DescriptorNeurturin, GDNF family receptor alpha-2, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
Functional Keywordscomplex, signalling, receptor, signaling protein
Biological sourceHomo sapiens (Human)
More
Cellular locationSecreted: Q99748
Cell membrane ; Lipid-anchor, GPI-anchor : O00451
Total number of polymer chains4
Total formula weight125522.36
Authors
Sandmark, J.,Oster, L.,Aagaard, A.,Roth, R.G.,Dahl, G. (deposition date: 2016-12-21, release date: 2018-01-17, Last modification date: 2024-11-13)
Primary citationSandmark, J.,Dahl, G.,Oster, L.,Xu, B.,Johansson, P.,Akerud, T.,Aagaard, A.,Davidsson, P.,Bigalke, J.M.,Winzell, M.S.,Rainey, G.J.,Roth, R.G.
Structure and biophysical characterization of the human full-length neurturin-GFRa2 complex: A role for heparan sulfate in signaling.
J. Biol. Chem., 293:5492-5508, 2018
Cited by
PubMed Abstract: Neurturin (NRTN) provides trophic support to neurons and is considered a therapeutic agent for neurodegenerative diseases, such as Parkinson's disease. It binds to its co-receptor GFRa2, and the resulting NRTN-GFRa2 complex activates the transmembrane receptors rearranged during transfection (RET) or the neural cell adhesion molecule (NCAM). We report the crystal structure of NRTN, alone and in complex with GFRa2. This is the first crystal structure of a GFRa with all three domains and shows that domain 1 does not interact directly with NRTN, but it may support an interaction with RET and/or NCAM, via a highly conserved surface. In addition, biophysical results show that the relative concentration of GFRa2 on cell surfaces can affect the functional affinity of NRTN through avidity effects. We have identified a heparan sulfate-binding site on NRTN and a putative binding site in GFRa2, suggesting that heparan sulfate has a role in the assembly of the signaling complex. We further show that mutant NRTN with reduced affinity for heparan sulfate may provide a route forward for delivery of NRTN with increased exposure in preclinical models and ultimately to Parkinson's patients.
PubMed: 29414779
DOI: 10.1074/jbc.RA117.000820
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.4 Å)
Structure validation

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