ArticleThe Journal of biological chemistry2015
Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Benchmarking porcine pancreatic ductal organoids for drug screening applications.EMBO molecular medicine · 2025Article
- Cryo-EM structure of the full-length LGR4-RSPOs complex and a targeting nanobody for anti-obesity therapy.Nature communications · 2025Article
- Distinct structural mechanisms of LGR4 modulation by Norrin and RSPOs in Wnt/β-catenin signaling.Nature communications · 2025Article
- RSPO1, a potent inducer of pancreatic β cell neogenesis.Cell reports. Medicine · 2025Article
- LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology.Biomedicines · 2025Review
- Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling.Nature communications · 2025Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Review: The evolution of peptidergic signaling in Cnidaria and Placozoa, including a comparison with Bilateria.Frontiers in endocrinology · 2022Review
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- LGR5 enhances the osteoblastic differentiation of MC3T3-E1 cells through the Wnt/β-catenin pathway.Experimental and therapeutic medicine · 2021Article
- Unlike LGR4, LGR5 potentiates Wnt-β-catenin signaling without sequestering E3 ligases.Science signaling · 2020Article
- LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma.Journal of clinical laboratory analysis · 2020Article
- The variable lymphocyte receptor as an antibody alternative.Current opinion in biotechnology · 2018Review
- Differential activities and mechanisms of the four R-spondins in potentiating Wnt/β-catenin signaling.The Journal of biological chemistry · 2018Article
- R-spondin3-LGR4 signaling protects hepatocytes against DMOG-induced hypoxia/reoxygenation injury through activating β-catenin.Biochemical and biophysical research communications · 2018Article
- Reactivity to Novel Autoantigens in Patients with Coexisting Central Nervous System Demyelinating Disease and Autoimmune Thyroid Disease.Frontiers in immunology · 2017Article
- LGR4 and Its Role in Intestinal Protection and Energy Metabolism.Frontiers in endocrinology · 2015Review
- In a Class of Their Own - RXFP1 and RXFP2 are Unique Members of the LGR Family.Frontiers in endocrinology · 2015Review
- Discovery and Development of Small Molecule Allosteric Modulators of Glycoprotein Hormone Receptors.Frontiers in endocrinology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs.
Indexed as
Identifiers
What OpenQuestion holds
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.