Amyloid fibril formation by αS1- and ß-casein implies that fibril formation is a general property of casein proteins.
Biochim Biophys Acta Proteins Proteom
; 1870(11-12): 140854, 2022 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-36087849
ABSTRACT
Caseins are a diverse family of intrinsically disordered proteins present in the milks of all mammals. A property common to two cow paralogues, αS2- and κ-casein, is their propensity in vitro to form amyloid fibrils, the highly ordered protein aggregates associated with many age-related, including neurological, diseases. In this study, we explored whether amyloid fibril-forming propensity is a general feature of casein proteins by examining the other cow caseins (αS1 and ß) as well as ß-caseins from camel and goat. Small-angle X-ray scattering measurements indicated that cow αS1- and ß-casein formed large spherical aggregates at neutral pH and 20°C. Upon incubation at 65°C, αS1- and ß-casein underwent conversion to amyloid fibrils over the course of ten days, as shown by thioflavin T binding, transmission electron microscopy, and X-ray fibre diffraction. At the lower temperature of 37°C where fibril formation was more limited, camel ß-casein exhibited a greater fibril-forming propensity than its cow or goat orthologues. Limited proteolysis of cow and camel ß-casein fibrils and analysis by mass spectrometry indicated a common amyloidogenic sequence in the proline, glutamine-rich, C-terminal region of ß-casein. These findings highlight the persistence of amyloidogenic sequences within caseins, which likely contribute to their functional, heterotypic self-assembly; in all mammalian milks, at least two caseins coalesce to form casein micelles, implying that caseins diversified partly to avoid dysfunctional amyloid fibril formation.
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MEDLINE
Assunto principal:
Caseínas
/
Proteínas Intrinsicamente Desordenadas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article