Review abstract
Nature Chemical Biology 5, 15 - 22 (2009)
Published online: 16 December 2008 | doi:10.1038/nchembio.131
Amyloid formation by globular proteins under native conditions
Fabrizio Chiti1 & Christopher M Dobson2
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.
- Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Viale Morgagni 50, I-50134 Firenze, Italy.
- Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Correspondence to: Fabrizio Chiti1 e-mail: fabrizio.chiti@unifi.it
Correspondence to: Christopher M Dobson2 e-mail: cmd44@cam.ac.uk.
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