ArticleThe Journal of biological chemistry2014
Investigation of interactions at the extracellular loops of the relaxin family peptide receptor 1 (RXFP1).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Divergent activation of the RXFP1 relaxin receptor by protein and small molecule agonists.bioRxiv : the preprint server for biology · 2026Article
- The relaxin receptor RXFP1 signals through a mechanism of autoinhibition.Nature chemical biology · 2023Article
- Characterization of a new potent and long-lasting single chain peptide agonist of RXFP1 in cells and in vivo translational models.Scientific reports · 2022Article
- Expression and Characterization of Relaxin Family Peptide Receptor 1 Variants.Frontiers in pharmacology · 2021Article
- The relaxin family peptide receptor 1 (RXFP1): An emerging player in human health and disease.Molecular genetics & genomic medicine · 2020Review
- Multi-Component Mechanism of H2 Relaxin Binding to RXFP1 through NanoBRET Kinetic Analysis.iScience · 2019Article
- Understanding GPCR Recognition and Folding from NMR Studies of Fragments.RSC advances · 2018Article
- In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis.Scientific reports · 2017Article
- Distinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin.Scientific reports · 2017Article
- Development of a selective agonist for relaxin family peptide receptor 3.Scientific reports · 2017Article
- ML290 is a biased allosteric agonist at the relaxin receptor RXFP1.Scientific reports · 2017Article
- Synthetic non-peptide low molecular weight agonists of the relaxin receptor 1.British journal of pharmacology · 2017Review
- Relaxin family peptides: structure-activity relationship studies.British journal of pharmacology · 2017Review
- Mechanism for insulin-like peptide 5 distinguishing the homologous relaxin family peptide receptor 3 and 4.Scientific reports · 2016Article
- A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1.Chemical science · 2016Article
- The complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1.Nature communications · 2016Article
- Structural Insights into the Activation of Human Relaxin Family Peptide Receptor 1 by Small-Molecule Agonists.Biochemistry · 2016Article
- Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).The Journal of biological chemistry · 2015Article
- In a Class of Their Own - RXFP1 and RXFP2 are Unique Members of the LGR Family.Frontiers in endocrinology · 2015Review
- Activation of Relaxin Family Receptor 1 from Different Mammalian Species by Relaxin Peptide and Small-Molecule Agonist ML290.Frontiers in endocrinology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Relaxin, an emerging pharmaceutical treatment for acute heart failure, activates the relaxin family peptide receptor (RXFP1), which is a class A G-protein-coupled receptor. In addition to the classic transmembrane (TM) domain, RXFP1 possesses a large extracellular domain consisting of 10 leucine-rich repeats and an N-terminal low density lipoprotein class A (LDLa) module. Relaxin-mediated activation of RXFP1 requires multiple coordinated interactions between the ligand and various receptor domains including a high affinity interaction involving the leucine-rich repeats and a predicted lower affinity interaction involving the extracellular loops (ELs). The LDLa is essential for signal activation; therefore the ELs/TM may additionally present an interaction site to facilitate this LDLa-mediated signaling. To overcome the many challenges of investigating relaxin and the LDLa module interactions with the ELs, we engineered the EL1 and EL2 loops onto a soluble protein scaffold, mapping specific ligand and loop interactions using nuclear magnetic resonance spectroscopy. Key EL residues were subsequently mutated in RXFP1, and changes in function and relaxin binding were assessed alongside the RXFP1 agonist ML290 to monitor the functional integrity of the TM domain of these mutant receptors. The outcomes of this work make an important contribution to understanding the mechanism of RXFP1 activation and will aid future development of small molecule RXFP1 agonists/antagonists.
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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.