Phase Separation and Fibrillization of Human Annexin A7 Are Mediated by Its Proline-Rich Domain.
Biochemistry
; 62(21): 3036-3040, 2023 11 07.
Article
em En
| MEDLINE
| ID: mdl-37788367
ABSTRACT
Human annexin A7, a calcium- and phospholipid-binding protein, governs calcium homeostasis, plasma membrane repair, apoptosis, and tumor progression. A7 contains an N-terminal proline-rich domain (PRD; 180 residues, â¼24% prolines) that determines its functional specificity. Using microscopy and dye-binding assays, we show that recombinant A7 and its isolated PRD spontaneously phase separate into spherical condensates, which subsequently transform into ß-sheet-rich fibrils. We demonstrate that fibrillization of A7-PRD proceeds via primary nucleation and fibril-catalyzed secondary nucleation processes, as determined by chemical kinetics, providing a mechanistic basis for its amyloid assembly. This study confirms and highlights a subclass of eukaryotic PRDs prone to forming aggregates with important physiological and pathological implications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Anexina A7
Limite:
Humans
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos