Secretory quality control constrains functional selection-associated protein structure innovation.
Commun Biol
; 5(1): 268, 2022 03 25.
Article
em En
| MEDLINE
| ID: mdl-35338247
ABSTRACT
Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína C-Reativa
/
Dobramento de Proteína
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2022
Tipo de documento:
Article