Anno2016
AutoriCamilloni C, Sala BM, Sormanni P, Porcari R, Corazza A, De Rosa M, Zanini S, Barbiroli A, Esposito G, Bolognesi M, Bellotti V, Vendruscolo M, Ricagno S
AbstractA wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (?2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed ?2m variants that alter the aggregation-prone exposed surface of wild-type and W60G ?2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in ?2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.
RivistaScientific Reports (nature Publishing Group)
ISSN2045-2322
Impact factor
Volume6
Pagina inizio
Pagina fine
Autori IBFMartino BOLOGNESI
Linee di Ricerca IBFMD.P01.005.001
Sedi IBFIBF.MI