ArticleThe Journal of biological chemistry2009
Pro-interleukin (IL)-1beta shares a core region of stability as compared with mature IL-1beta while maintaining a distinctly different configurational landscape: a comparative hydrogen/deuterium exchange mass spectrometry study.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Post-translational control of IL-1β via the human papillomavirus type 16 E6 oncoprotein: a novel mechanism of innate immune escape mediated by the E3-ubiquitin ligase E6-AP and p53.PLoS pathogens · 2013Trial
- A moonlighting function of tumoral interleukin-1β precursor promotes metastasis via RACK1-mediated actin remodeling.Nature communications · 2025Article
- Virtual Screening and Molecular Dynamics of Cytokine-Drug Complexes for Atherosclerosis Therapy.International journal of molecular sciences · 2025Article
- Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β.Nature communications · 2023Article
- Redox-dependent gating of VDAC by mitoNEET.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- An innate interaction between IL-18 and the propeptide that inactivates its precursor form.Scientific reports · 2019Article
- Redefining the ancestral origins of the interleukin-1 superfamily.Nature communications · 2018Article
- HMGB1/IL-1β complexes in plasma microvesicles modulate immune responses to burn injury.PloS one · 2018Article
- Association of the Precursor of Interleukin-1β and Peritoneal Inflammation-Role in Pathogenesis of Endometriosis.Journal of clinical laboratory analysis · 2016Article
- Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation.Nature communications · 2015Article
- Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of-Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)-Dependent Inflammatory Response.The Journal of biological chemistry · 2015Article
- Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Allosteric switching of agonist/antagonist activity by a single point mutation in the interluekin-1 receptor antagonist, IL-1Ra.Journal of molecular biology · 2013Article
- Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders.Molecular psychiatry · 2013Article
- Regulating SR protein phosphorylation through regions outside the kinase domain of SRPK1.Journal of molecular biology · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-1beta (IL-1beta) is a master cytokine involved in initiating the innate immune response in vertebrates (Dinarello, C. A. (1994) FASEB J. 8, 1314-1325). It is first synthesized as an inactive 269-residue precursor (pro-interleukin-1beta or pro-IL-1beta). Pro-IL-1beta requires processing by caspase-1 to generate the active, mature 153-residue cytokine. In this study, we combined hydrogen/deuterium exchange mass spectrometry, circular dichroism spectroscopy, and enzymatic digestion comparative studies to investigate the configurational landscape of pro-IL-1beta and the role the N terminus plays in modulating the landscape. We find that the N terminus keeps pro-IL-1beta in a protease-labile state while maintaining a core region of stability in the C-terminal region, the eventual mature protein. In mature IL-1beta, this highly protected region maps back to the area protected earliest in the NMR studies characterizing an on-route kinetic refolding intermediate. This protected region also encompasses two important functional loops that participate in the IL-1beta/receptor binding interface required for biological activity. We propose that the purpose of the N-terminal precursor region in pro-IL-1beta is to suppress the function of the eventual mature region while keeping a structurally and also functionally important core region primed for the final folding into the native, active state of the mature protein. The presence of the self-inhibiting precursor region provides yet another layer of regulation in the life cycle of this important cytokine.
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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.