Experimental basis for a new allosteric model for multisubunit proteins.
Proc Natl Acad Sci U S A
; 111(35): 12758-63, 2014 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-25139985
ABSTRACT
Monod, Wyman, and Changeux (MWC) explained allostery in multisubunit proteins with a widely applied theoretical model in which binding of small molecules, so-called allosteric effectors, affects reactivity by altering the equilibrium between more reactive (R) and less reactive (T) quaternary structures. In their model, each quaternary structure has a single reactivity. Here, we use silica gels to trap protein conformations and a new kind of laser photolysis experiment to show that hemoglobin, the paradigm of allostery, exhibits two ligand binding phases with the same fast and slow rates in both R and T quaternary structures. Allosteric effectors change the fraction of each phase but not the rates. These surprising results are readily explained by the simplest possible extension of the MWC model to include a preequilibrium between two tertiary conformations that have the same functional properties within each quaternary structure. They also have important implications for the long-standing question of a structural explanation for the difference in hemoglobin oxygen affinity of the two quaternary structures.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemoglobina A
/
Hemoglobinas
/
Modelos Químicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article