ArticlePloS one2012
The unique cysteine knot regulates the pleotropic hormone leptin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 53 citations in OpenAlex.
- Tangled Tail of Mechanically Interlocked Peptides.Journal of the American Chemical Society · 2026Review
- Detecting misfolded non-covalent lasso entanglements in protein structures, simulation trajectories, and mass spectrometry data.bioRxiv : the preprint server for biology · 2026Article
- Bioinformatic Analysis of the Leptin-Ob-R Interface: Structural Modeling, Thermodynamic Profiling, and Stability in Diverse Microenvironments.International journal of molecular sciences · 2025Article
- How synonymous mutations alter enzyme structure and function over long timescales.Nature chemistry · 2023Article
- In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata.PloS one · 2022Article
- Lasso Proteins-Unifying Cysteine Knots and Miniproteins.Polymers · 2021Article
- Slipknotted and unknotted monovalent cation-proton antiporters evolved from a common ancestor.PLoS computational biology · 2021Article
- Topoly: Python package to analyze topology of polymers.Briefings in bioinformatics · 2021Article
- GLN: a method to reveal unique properties of lasso type topology in proteins.Scientific reports · 2020Article
- Searching the Optimal Folding Routes of a Complex Lasso Protein.Biophysical journal · 2019Article
- Uncovering the molecular mechanisms behind disease-associated leptin variants.The Journal of biological chemistry · 2018Article
- Estimated prevalence of potentially damaging variants in the leptin gene.Molecular and cellular pediatrics · 2017Article
- The Leptin Receptor Complex: Heavier Than Expected?Frontiers in endocrinology · 2017Review
- Complex lasso: new entangled motifs in proteins.Scientific reports · 2016Article
- LassoProt: server to analyze biopolymers with lassos.Nucleic acids research · 2016Article
- Quack leptin.BMC genomics · 2014Article
- Pierced Lasso Bundles are a new class of knot-like motifs.PLoS computational biology · 2014Article
- Molecular dynamics, dynamic site mapping, and highthroughput virtual screening on leptin and the Ob receptor as anti-obesity target.Journal of molecular modeling · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin.
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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.