ArticleNature structural & molecular biology2023
Mechanism of receptor assembly via the pleiotropic adipokine Leptin.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Circuit Mechanisms Underlying the Contribution of Leptin Receptor-Expressing Neurons in the Nucleus Tractus Solitarius to Ventilatory Homeostasis.Neuroscience bulletin · 2026Article
- Single-Molecule FRET-Tracking of InlB-Activated MET Receptors in Living Cells.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Structural and functional characterization of the Pro64Ser leptin mutant: Implications for congenital leptin deficiency.Biophysical journal · 2025Article
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Systemic and Local Leptin Resistance in Patients with Cardiovascular Diseases.Diagnostics (Basel, Switzerland) · 2025Article
- Leptin as a key driver for organ fibrogenesis.Science advances · 2025Article
- Bioinformatic Analysis of the Leptin-Ob-R Interface: Structural Modeling, Thermodynamic Profiling, and Stability in Diverse Microenvironments.International journal of molecular sciences · 2025Article
- Meteorin-β: A Novel Biomarker and Therapeutic Target on Its Way to the Regulation of Human Diseases.International journal of molecular sciences · 2025Review
- A brown fat-enriched adipokine, ASRA, is a leptin receptor antagonist that stimulates appetite.bioRxiv : the preprint server for biology · 2024Article
- Regulation of leptin signaling and diet-induced obesity by SEL1L-HRD1 ER-associated degradation in POMC expressing neurons.Nature communications · 2024Article
- Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.Molecular cell · 2024Article
- Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23.Nature structural & molecular biology · 2024Article
- SEL1L-HRD1 ER-associated degradation regulates leptin receptor maturation and signaling in POMC neurons in diet-induced obesity.Research square · 2024Article
- Structural Modeling of Cytokine-Receptor-JAK2 Signaling Complexes Using AlphaFold Multimer.Journal of chemical information and modeling · 2023Article
- Structural modeling of cytokine-receptor-JAK2 signaling complexes using AlphaFold Multimer.bioRxiv : the preprint server for biology · 2023Article
- Structural insights into the mechanism of leptin receptor activation.Nature communications · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and cancer. However, the structure and mechanism of Leptin-mediated LEP-R assemblies has remained unclear. Intriguingly, the signaling-competent isoform of LEP-R is only lowly abundant amid several inactive short LEP-R isoforms contributing to a mechanistic conundrum. Here we show by X-ray crystallography and cryo-EM that, in contrast to long-standing paradigms, Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry and demonstrate such Leptin-induced trimerization of LEP-R on living cells via single-molecule microscopy. In mediating these assemblies, Leptin undergoes drastic restructuring that activates its site III for binding to the Ig domain of an adjacent LEP-R. These interactions are abolished by mutations linked to obesity. Collectively, our study provides the structural and mechanistic framework for how evolutionarily conserved Leptin:LEP-R assemblies with 3:3 stoichiometry can engage distinct LEP-R isoforms to achieve signaling.
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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.