ArticleThe Journal of biological chemistry2018
Structure and biophysical characterization of the human full-length neurturin-GFRa2 complex: A role for heparan sulfate in signaling.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- A long-chain heparan sulfate capture mechanism directs paracrine GDNF-GFRα1 signalling through RET.bioRxiv : the preprint server for biology · 2026Article
- RET receptor tyrosine kinase architecture, assemblies, and activation.Endocrine-related cancer · 2026Review
- Secondary analysis of GenRED data (Genetics of Recurrent Early-Onset major Depression) using MERLIN.European archives of psychiatry and clinical neuroscience · 2026Article
- Analysis of Transcriptome and Differentially Expressed Genes in Chicken Primordial Germ Cells.Animals : an open access journal from MDPI · 2026Article
- Proteome-wide Mendelian randomization and colocalization analysis uncovers druggable targets for lung cancer across multiple phenotypes and complications.Discover oncology · 2025Article
- Design of Bicyclic Peptide Tandems Mimicking the Homodimeric GDF15 Protein to Inhibit GDF15-GFRaL-RET Complex Cell Signaling.Journal of medicinal chemistry · 2025Article
- Spatial transcriptomics exploration of the primary neuroblastoma microenvironment in archived FFPE samples unveils novel paracrine interactions.The Journal of pathology · 2025Article
- Lipidomic and transcriptomic profiling reveal alterations in the coexistence of gestational diabetes mellitus and preeclampsia impacting maternal and neonatal outcomes.Scientific reports · 2025Article
- Article
- Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly.Nature communications · 2023Article
- Article
- Identification of Candidate Genes for Min Pig Villi Hair Traits by Genome-Wide Association of Copy Number Variation.Veterinary sciences · 2023Article
- Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures.NPJ Parkinson's disease · 2022Article
- Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.Developmental cell · 2022Article
- Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism.Molecular psychiatry · 2022Review
- The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers.International journal of medical sciences · 2022Review
- A two-site flexible clamp mechanism for RET-GDNF-GFRα1 assembly reveals both conformational adaptation and strict geometric spacing.Structure (London, England : 1993) · 2021Article
- Protection of dopamine neurons by CDNF and neurturin variant N4 against MPP+ in dissociated cultures from rat mesencephalon.PloS one · 2021Article
- Improving therapeutic potential of GDNF family ligands.Cell and tissue research · 2020Review
- Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.