INVESTIGADORES
FERREIRO Diego Ulises
artículos
Título:
The energy landscape of modular repeat proteins: topology determines folding mechanism in the ankyrin family.
Autor/es:
FERREIRO DU, CHO SS, KOMIVES EA, WOLYNES PG.
Revista:
JOURNAL OF MOLECULAR BIOLOGY
Referencias:
Año: 2005 vol. 354 p. 679 - 692
ISSN:
0022-2836
Resumen:
Proteins consisting of repeating amino acid motifs are abundant in all kingdoms of life, especially in higher eukaryotes. Repeat-containing proteins self-organize into elongated non-globular structures. Do the same general underlying principles that dictate the folding of globular domains apply also to these extended topologies? Using a simplified structure-based model capturing a perfectly funneled energy landscape, we surveyed the predicted mechanism of folding for ankyrin repeat containing proteins. The ankyrin family is one of the most extensively studied classes of non-globular folds. The model based only on native contacts reproduces most of the experimental observations on the folding of these proteins, including a folding mechanism that is reminiscent of a nucleation propagation growth. The confluence of simulation and experimental results suggests that the folding of non-globular proteins is accurately described by a funneled energy landscape, in which topology plays a determinant role in the folding mechanism.