Local transient unfolding of native state PAI-1 associated with serpin metastability.
Angew Chem Int Ed Engl
; 53(37): 9751-4, 2014 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-25049220
ABSTRACT
The metastability of the native fold makes serpin (serine protease inhibitor) proteins prone to pathological conformational change, often by insertion of an extra ß-strand into the central ß-sheet A. How this insertion is made possible is a hitherto unresolved question. By the use of advanced hydrogen/deuterium-exchange mass spectrometry (HDX-MS) it is shown that the serpin plasminogen activator inhibitor 1 (PAI-1) transiently unfolds under native condition, on a second-to-minute time scale. The unfolding regions comprise ß-strand 5A as well as the underlying hydrophobic core, including ß-strand 6B and parts of helicesâ
A, B, and C. Based thereon, a mechanism is proposed by which PAI-1 makes transitions through progressively more unfolded states along the reaction coordinate to the inactive, so-called latent form. Our results highlight the profound utility of HDX-MS in detecting sparsely populated, transiently unfolded protein states.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidor 1 de Ativador de Plasminogênio
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2014
Tipo de documento:
Article