ArticleThe Journal of biological chemistry2013
The structure of irisin reveals a novel intersubunit β-sheet fibronectin type III (FNIII) dimer: implications for receptor activation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed.
- Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.Cell metabolism · 2014Trial
- Irisin upregulation as a contributory mechanism for the therapeutic benefits of SGLT-2 inhibitors.Pharmacology & therapeutics · 2026Review
- Reduced serum Irisin levels in systemic sclerosis: a cross-sectional case-control study.Clinical rheumatology · 2026Article
- Seasonal fluctuations in the hypothalamic irisin and its correlation with the hypothalamic-pituitary-gonadal -axis activity in male rhesus monkeys (Macaca mulatta).Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.Biogerontology · 2026Review
- Anastellin: A Fibronectin-Derived Peptide Targeting the Tumor Microenvironment Through ECM Modulation.Cell biochemistry and biophysics · 2026Review
- Exercise-Induced Irisin: A Novel Strategy for Neuroinflammation Alleviation and Neurorepair in Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Protective Role of Physical Exercise and Exercise-Induced FNDC5/Irisin in Combating Diabetes-Related Cognitive Impairment and Autonomic and Peripheral Neuropathies: A Comprehensive Review.Journal of diabetes research · 2026Review
- Molecular insights into irisin's role in the regulation of programmed cell death: mechanisms and therapeutic potential.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Developing Subcutaneous Formulations for Irisin as a Potential Therapeutic.Pharmaceutical research · 2025Article
- Irisin deficiency exacerbates cardiac dysfunction and enhances hemorrhage injury in hemorrhage/resuscitation.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Irisin, the Myokine: Guardian and Mediator in Cardiovascular System.Endocrinology, diabetes & metabolism · 2025Review
- Diagnostic and Therapeutic Value of the Exercise-Induced Myokine Irisin in Cancer Biology: A Comprehensive Review.Diseases (Basel, Switzerland) · 2025Review
- Irisin: muscle's novel player in endoplasmic reticulum stress and disease.Molecular and cellular biochemistry · 2025Review
- Potential role of FNDC5 in exercise-induced improvement of cognitive function.Journal of Zhejiang University. Science. B · 2025Review
- Effects of Aerobic Exercise on Irisin and Skeletal Muscle Autophagy inCurrent issues in molecular biology · 2025Article
- Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Gold nanoparticles-conjugation of irisin enhances therapeutic effect by improving cardiac function and attenuating inflammation in sepsis.Molecular diversity · 2025Article
- Identification of candidate nsSNPs of the human FNDC5 gene and their structural and functional consequences using in silico analysis.Scientific reports · 2025Article
- Irisin-mediated KEAP1 degradation alleviates oxidative stress and ameliorates pancreatitis.Immunologic research · 2025Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
Irisin was recently identified as a putative myokine that is induced by exercise. Studies suggest that it is produced by cleavage of the FNDC5 (fibronectin domain-containing protein 5) receptor; irisin corresponds to the extracellular receptor ectodomain. Data suggesting that irisin stimulates white-to-brown fat conversion have led to the hypothesis that it does so by binding an unknown receptor, thus functioning as a myokine. As brown fat promotes energy dissipation, myokines that elicit the transformation of white to brown fat have potentially profound benefits in the treatment of obesity and metabolic disorders. Understanding the molecular basis for such exercise-induced phenomena is thus of considerable interest. Moreover, FNDC5-like receptors are highly conserved and have been shown to be critical for neuronal development. However, the structural and molecular mechanisms utilized by these proteins are currently unknown. Here, we describe the crystal structure and biochemical characterization of the FNDC5 ectodomain, corresponding to the irisin myokine. The 2.28 Å structure shows that irisin consists of an N-terminal fibronectin III (FNIII)-like domain attached to a flexible C-terminal tail. Strikingly, the FNIII-like domain forms a continuous intersubunit β-sheet dimer, previously unobserved for any FNIII protein. Biochemical data confirm that irisin is a dimer and that dimerization is unaffected by glycosylation. This finding suggests a possible mechanism for receptor activation by the irisin domain as a preformed myokine dimer ligand or as a paracrine or autocrine dimerization module on FNDC5-like receptors.
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