NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer.
FEBS Lett
; 515(1-3): 165-70, 2002 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-11943215
ABSTRACT
Nuclear magnetic resonance (NMR) spectroscopy reveals that higher-order aggregates of glucagon-like peptide-1-(7-36)-amide (GLP-1) in pure water at pH 2.5 are disrupted by 35% 2,2,2-trifluoroethanol (TFE), and form a stable and highly symmetric helical self-aggregate. NMR spectra show that the helical structure is identical to that formed by monomeric GLP-1 under the same experimental conditions [Chang et al., Magn. Reson. Chem. 37 (2001) 477-483; Protein Data Bank at RCSB code 1D0R], while amide proton exchange rates reveal a dramatic increase of the stability of the helices of the self-aggregate. Pulsed-field gradient NMR diffusion experiments show that the TFE-induced helical self-aggregate is a dimer. The experimental data and model calculations indicate that the dimer is a parallel coiled coil, with a few hydrophobic residues on the surface that may cause aggregation in pure water. The results suggest that the coiled coil dimer is an intermediate state towards the formation of higher aggregates, e.g. fibrils.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Precursores de Proteínas
/
Glucagón
/
Espectroscopía de Resonancia Magnética
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
FEBS Lett
Año:
2002
Tipo del documento:
Article
País de afiliación:
Dinamarca