Heparin promotes rapid fibrillation of the basic parathyroid hormone at physiological pH

FEBS Letters

article

Luca M. Lauth¹  Bruno Voigt²  Twinkle Bhatia¹  Lisa Machner³  Jochen Balbach²  Maria Ott² 

[1] Department of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg;Department of Biophysics, Martin-Luther-University Halle-Wittenberg;Department of Molecular Medicine, Martin-Luther-University Halle-Wittenberg

关键词: acidic pH;    amyloid fibrillation;    functional amyloids;    heparin interaction;    intrinsically disordered proteins;    parathyroid hormone;   

DOI  :  10.1002/1873-3468.14455

来源: John Wiley & Sons Ltd.

【 摘 要 】

In acidic secretory granules of mammalian cells, peptide hormones including the parathyroid hormone are presumably stored in the form of functional amyloid fibrils. Mature PTH, however, is considerably positively charged in acidic environments, a condition known to impede unassisted self-aggregation into fibrils. Here, we studied the role of the polyanion heparin on promoting fibril formation of PTH. Employing ITC, CD spectroscopy, NMR, SAXS, and fluorescence-based assays, we could demonstrate that heparin binds PTH with submicromolar affinity and facilitates its conversion into fibrillar seeds, enabling rapid formation of amyloid fibrils under acidic conditions. In the absence of heparin, PTH remained in a soluble monomeric state. We suspect that heparin-like surfaces are required in vivo to convert PTH efficiently into fibrillar deposits.

【 授权许可】

Unknown