English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/156899
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

The effect of electrostatics on the marginal cooperativity of an ultrafast folding protein

AutorDesai, Tanay M.; Cerminara, Michele; Sadqi, Mourad; Muñoz van den Eynde, Víctor
Palabras claveBiophysics
Cooperativity
Protein conformation
Protein folding
Protein stability
Downhill folding
Electrostatic screening
Ultrafast kinetics
Fecha de publicación5-nov-2010
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónThe Journal of Biological Chemistry 285 (45) 34549–34556 (2010)
ResumenProteins fold up by coordinating the different segments of their polypeptide chain through a network of weak cooperative interactions. Such cooperativity results in unfolding curves that are typically sigmoidal. However, we still do not know what factors modulate folding cooperativity or the minimal amount that ensures folding into specific three-dimensional structures. Here, we address these issues on BBL, a small helical protein that folds in microseconds via a marginally cooperative downhill process (Li, P., Oliva, F. Y., Naganathan, A. N., and Muñoz, V. (2009) Proc. Natl. Acad. Sci. USA. 106, 103-108). Particularly, we explore the effects of salt-induced screening of the electrostatic interactions in BBL at neutral pH and in acid-denatured BBL. Our results show that electrostatic screening stabilizes the native state of the neutral and protonated forms, inducing complete refolding of acid-denatured BBL. Furthermore, without net electrostatic interactions, the unfolding process becomes much less cooperative, as judged by the broadness of the equilibrium unfolding curve and the relaxation rate. Our experiments show that the marginally cooperative unfolding of BBL can still be made twice as broad while the protein retains its ability to fold into the native three-dimensional structure in microseconds. This result demonstrates experimentally that efficient folding does not require cooperativity, confirming predictions from theory and computer simulations and challenging the conventional biochemical paradigm. Furthermore, we conclude that electrostatic interactions are an important factor in determining folding cooperativity. Thus, electrostatic modulation by pH-salt and/or mutagenesis of charged residues emerges as an attractive tool for tuning folding cooperativity.
Descripción13 p.-5 fig.-1 tab.-3 fig. supl.-1 tab. supl.
Versión del editorhttp://dx.doi.org/10.1074/jbc.M110.154021
URIhttp://hdl.handle.net/10261/156899
DOI10.1074/jbc.M110.154021
ISSN0021-9258
E-ISSN1083-351X
Aparece en las colecciones: (CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
J. Biol. Chem.-2010-Desai-34549-56.pdfArtículo principal + material suplementario2,9 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.