Local unfolding and aggregation mechanisms of SOD1: a Monte Carlo exploration.
J Phys Chem B
; 117(31): 9194-202, 2013 Aug 08.
Article
en En
| MEDLINE
| ID: mdl-23844996
Copper, zinc superoxide dismutase 1 (SOD1) is a ubiquitous homodimeric enzyme, whose misfolding and aggregation play a potentially key role in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). SOD1 aggregation is thought to be preceded by dimer dissociation and metal loss, but the mechanisms by which the metal-free monomer aggregates remain incompletely understood. Here we use implicit solvent all-atom Monte Carlo (MC) methods to investigate the local unfolding dynamics of the ß-barrel-forming SOD1 monomer. Although event-to-event variations are large, on average, we find clear differences in dynamics among the eight strands forming the ß-barrel. Most dynamic is the eighth strand, ß8, which is located in the dimer interface of native SOD1. For the four strands in or near the dimer interface (ß1, ß2, ß7, and ß8), we perform aggregation simulations to assess the propensity of these chain segments to self-associate. We find that ß1 and ß2 readily self-associate to form intermolecular parallel ß-sheets, whereas ß8 shows a very low aggregation propensity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
Tipo de estudio:
Health_economic_evaluation
Límite:
Humans
Idioma:
En
Revista:
J Phys Chem B
Asunto de la revista:
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos