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Title: The pro-sequence of parathyroid hormone prevents premature amyloid fibril formation
Author(s): Sachan, Shubhra
Gonzalez Moya, Celia
Voigt, Bruno
Köhn, Marcel
Balbach, JochenLook up in the Integrated Authority File of the German National Library
Issue Date: 2023
Type: Article
Language: English
Abstract: The parathyroid hormone (PTH) regulates the calcium and phosphate level in blood after secretion from parathyroid chief cells. The pre- and pro-sequences of precursor preproPTH get cleaved during PTH maturation. In secretory granules, PTH forms functional amyloids. Using thioflavin T fibrillation assays, circular dichroism, NMR spectroscopy, and cellular cAMP activation, we show that the pro-sequence prevents premature fibrillation by impairing primary nucleation because of Coulomb repulsion of positively charged residues. Under seeding or high salt conditions or in the presence of heparin at pH 5.5, proPTH fibril formation is delayed, but the monomer release properties are conserved. ProPTH can still activate in cellulo PTH receptor 1 but with impaired potency. These findings give some perspectives on medical applications of PTH in hormone therapy.
Open Access: Open access publication
License: (CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0(CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0
Journal Title: FEBS letters
Publisher: Wiley
Publisher Place: Chichester
Volume: 597
Issue: 7
Original Publication: 10.1002/1873-3468.14587
Page Start: 995
Page End: 1006
Appears in Collections:Open Access Publikationen der MLU