Insulin solubility transitions by pH-dependent interactions with proinsulin C-peptide
Autor: | Hanna Willander, Michael Landreh, Jan-Bernd Stukenborg, Hans Jörnvall, Gunvor Alvelius, Jan Johansson, Olle Söder |
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Rok vydání: | 2012 |
Předmět: |
chemistry.chemical_classification
C-Peptide C-peptide Insulin medicine.medical_treatment Peptide Cell Biology Hydrogen-Ion Concentration Biochemistry chemistry.chemical_compound chemistry Solubility medicine Humans Protein quaternary structure Secretion Molecular Biology Insulin processing Proinsulin |
Zdroj: | The FEBS journal. 279(24) |
ISSN: | 1742-4658 |
Popis: | Proinsulin processing into insulin and C-peptide in the secretory granules of the pancreatic β-cells occurs under mildly acidic conditions and at high peptide concentrations (> 10 mm). Mature insulin has reduced solubility and a propensity to adopt an amyloid-like structure, but is physiologically released as a mixture of a zinc-containing core and a zinc-free, C-peptide-rich fluid phase. C-peptide is known to function in the insulin secretion, but its exact mode of interaction is not established. We now demonstrate that C-peptide in sub-stoichiometric amount versus insulin coprecipitates with insulin at the pH found in secretory vesicles. Precipitation is reversible and the precipitate is dissolved by elevation of the pH. This effect was found to be dependent on relatively conserved glutamate residues in the otherwise poorly conserved C-peptide. Together, the data show that C-peptide has the ability to influence insulin solubility. The physiological pH changes between insulin processing and release sites may therefore affect the quaternary structure of insulin, as well as the phase transitions during insulin sorting and secretion. Structured digital abstract Insulin and C-peptide bind by molecular sieving (View Interaction: 1, 2) C-peptide and Insulin bind by dynamic light scattering (View Interaction: 1, 2) C-peptide and Insulin bind by fluorescence technology (View Interaction: 1, 2, 3, 4) |
Databáze: | OpenAIRE |
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