The conversion of proteins from their soluble states into well-organized fibrillar aggregates is associated with a wide range of pathological conditions, including neurodegenerative diseases and systemic amyloidoses. In this review, we discuss the mechanism of aggregation of globular proteins under conditions in which they are initially folded. Although a conformational change of the native state is generally necessary to initiate aggregation, we show that a transition across the major energy barrier for unfolding is not essential and that aggregation may well be initiated from locally unfolded states that become accessible, for example, via thermal fluctuations occurring under physiological conditions. We review recent evidence on this topic and discuss its significance for understanding the onset and potential inhibition of protein aggregation in the context of diseases.

Amyloid formation by globular proteins under native conditions / F.CHITI; C.M.DOBSON. - In: NATURE CHEMICAL BIOLOGY. - ISSN 1552-4450. - STAMPA. - 5:(2009), pp. 15-22. [10.1038/nchembio.131]

Amyloid formation by globular proteins under native conditions

CHITI, FABRIZIO;
2009

Abstract

The conversion of proteins from their soluble states into well-organized fibrillar aggregates is associated with a wide range of pathological conditions, including neurodegenerative diseases and systemic amyloidoses. In this review, we discuss the mechanism of aggregation of globular proteins under conditions in which they are initially folded. Although a conformational change of the native state is generally necessary to initiate aggregation, we show that a transition across the major energy barrier for unfolding is not essential and that aggregation may well be initiated from locally unfolded states that become accessible, for example, via thermal fluctuations occurring under physiological conditions. We review recent evidence on this topic and discuss its significance for understanding the onset and potential inhibition of protein aggregation in the context of diseases.
5
15
22
F.CHITI; C.M.DOBSON
File in questo prodotto:
File Dimensione Formato  
paper.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: DRM non definito
Dimensione 813.93 kB
Formato Adobe PDF
813.93 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/347470
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 670
  • ???jsp.display-item.citation.isi??? 639
social impact