ArticleProtein science : a publication of the Protein Society2003
pH Dependence of structural stability of interleukin-2 and granulocyte colony-stimulating factor.
Article in Protein science : a publication of the Protein Society, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 37 citations in OpenAlex.
- The T-Cell Growth Factor Interleukin-2, Which Is Occasionally Targeted by Autoantibodies, Qualifies as Drug for the Treatment of Allergy, Autoimmunity, and Cancer: Collegium Internationale Allergologicum (CIA) Update 2024.International archives of allergy and immunology · 2024Review
- Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity.Signal transduction and targeted therapy · 2023Article
- Temperature- and pH-Responsive Polymeric Photocatalysts for Enhanced Control and Recovery.Angewandte Chemie (International ed. in English) · 2022Review
- pH induced conformational alteration in human peroxiredoxin 6 might be responsible for its resistance against lysosomal pH or high temperature.Scientific reports · 2021Article
- Effects of Excipients on the Structure and Dynamics of Filgrastim Monitored by Thermal Unfolding Studies by CD and NMR Spectroscopy.ACS omega · 2020Article
- Purification of target proteins from intracellular inclusions mediated by intein cleavable polyhydroxyalkanoate synthase fusions.Microbial cell factories · 2017Article
- Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR.Pharmaceutical research · 2015Article
- Gathering support for critical mass: interleukin 4 receptor signaling requires clustering in endosomes.Biophysical journal · 2014Article
- Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method.International journal of nanomedicine · 2012Article
- Surgical wound healing using hemostatic gauze scaffold loaded with nanoparticles containing sustained-release granulocyte colony-stimulating factor.International journal of nanomedicine · 2011Article
- Optimization and applications of CDAP labeling for the assignment of cysteines.Pharmaceutical research · 2005Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After a cytokine binds to its receptor on the cell surface (pH approximately 7), the complex is internalized into acidic endosomal compartments (pH approximately 5-6), where partially unfolded intermediates can form. The nature of these structural transitions was studied for wild-type interleukin-2 (IL-2) and wild-type granulocyte colony-stimulating factor (G-CSF). A noncoincidence of denaturation transitions in the secondary and tertiary structure of IL-2 and tertiary structural perturbations in G-CSF suggest the presence of an intermediate state for each, a common feature of this structural family of four-helical bundle proteins. Unexpectedly, both IL-2 and G-CSF display monotonic increases in stability as the pH is decreased from 7 to 4. We hypothesize that such cytokines with cell-based clearance mechanisms in vivo may have evolved to help stabilize endosomal complexes for sorting to lysosomal degradation. We show that mutants of both IL-2 and G-CSF have differential stabilities to their wild-type counterparts as a function of pH, and that these differences may explain the differences in ligand trafficking and depletion. Further understanding of the structural changes accompanying unfolding may help guide cytokine design with respect to ligand binding, endocytic trafficking, and, consequently, therapeutic efficacy.
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