Heparin promotes rapid fibrillation of the basic parathyroid hormone at physiological pH.
FEBS Lett
; 596(22): 2928-2939, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35903816
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Heparina
/
Amiloide
Limite:
Animals
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha