Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions.
J Am Chem Soc
; 135(27): 10155-63, 2013 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-23758617
ABSTRACT
Intrinsically disordered proteins (IDPs) are widespread and important in biology but defy the classical protein structure-function paradigm by being functional in the absence of a stable, folded conformation. Here we investigate the coupling between transient secondary and tertiary structure in the protein activator for thyroid hormone and retinoid receptors (ACTR) by rationally modulating the helical propensity of a partially formed α-helix via mutations. Eight mutations predicted to affect the population of a transient helix were produced and investigated by NMR spectroscopy. Chemical shift changes distant to the mutation site are observed in regions containing other transient helices indicating that distant helices are stabilized through long-range hydrophobic helix-helix interactions and demonstrating the coupling of transient secondary and tertiary structure. The long-range structure of ACTR is also probed using paramagnetic relaxation enhancements (PRE) and residual dipolar couplings, which reveal an additional long-range contact between the N- and C-terminal segments. Compared to residual dipolar couplings and PRE, modulation of the helical propensity by mutagenesis thus reveals a different set of long-range interactions that may be obscured by stronger interactions that dominate other NMR measurements. This approach thus offers a complementary and generally applicable strategy for probing long-range structure in disordered proteins.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Intrínsecamente Desordenadas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Año:
2013
Tipo del documento:
Article
País de afiliación:
Dinamarca