Structure, Folding Dynamics, and Amyloidogenesis of D76N beta(2)-Microglobulin ROLES OF SHEAR FLOW, HYDROPHOBIC SURFACES, AND alpha-CRYSTALLIN (Articolo in rivista)

Type
Label
  • Structure, Folding Dynamics, and Amyloidogenesis of D76N beta(2)-Microglobulin ROLES OF SHEAR FLOW, HYDROPHOBIC SURFACES, AND alpha-CRYSTALLIN (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1074/jbc.M113.498857 (literal)
Alternative label
  • Mangione, P. Patrizia; Esposito, Gennaro; Relini, Annalisa; Raimondi, Sara; Porcari, Riccardo; Giorgetti, Sofia; Corazza, Alessandra; Fogolari, Federico; Penco, Amanda; Goto, Yuji; Lee, Young-Ho; Yagi, Hisashi; Cecconi, Ciro; Naqvi, Mohsin M.; Gillmore, Julian D.; Hawkins, Philip N.; Chiti, Fabrizio; Rolandi, Ranieri; Taylor, Graham W.; Pepys, Mark B.; Stoppini, Monica; Bellotti, Vittorio (2013)
    Structure, Folding Dynamics, and Amyloidogenesis of D76N beta(2)-Microglobulin ROLES OF SHEAR FLOW, HYDROPHOBIC SURFACES, AND alpha-CRYSTALLIN
    in The Journal of biological chemistry (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Mangione, P. Patrizia; Esposito, Gennaro; Relini, Annalisa; Raimondi, Sara; Porcari, Riccardo; Giorgetti, Sofia; Corazza, Alessandra; Fogolari, Federico; Penco, Amanda; Goto, Yuji; Lee, Young-Ho; Yagi, Hisashi; Cecconi, Ciro; Naqvi, Mohsin M.; Gillmore, Julian D.; Hawkins, Philip N.; Chiti, Fabrizio; Rolandi, Ranieri; Taylor, Graham W.; Pepys, Mark B.; Stoppini, Monica; Bellotti, Vittorio (literal)
Pagina inizio
  • 30917 (literal)
Pagina fine
  • 30930 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 288 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 14 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 43 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University College London; University of Pavia; University of Udine; University of Genoa; Osaka University; Consiglio Nazionale delle Ricerche (CNR); Universita di Modena e Reggio Emilia; University of Florence (literal)
Titolo
  • Structure, Folding Dynamics, and Amyloidogenesis of D76N beta(2)-Microglobulin ROLES OF SHEAR FLOW, HYDROPHOBIC SURFACES, AND alpha-CRYSTALLIN (literal)
Abstract
  • Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human beta(2)-microglobulin (beta(2)m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N beta(2)m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type beta(2)m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it