Molecular recycling within amyloid fibrils

Natàlia Carulla, Gemma L. Caddy, Damien R. Hall, Jesús Zurdo, Margarida Gairí, Miguel Feliz, Ernest Giralt, Carol V. Robinson and Christopher M. Dobson ()
Additional contact information
Natàlia Carulla: University of Cambridge
Gemma L. Caddy: University of Cambridge
Damien R. Hall: University of Cambridge
Jesús Zurdo: University of Cambridge
Margarida Gairí: Parc Científic de Barcelona
Miguel Feliz: Parc Científic de Barcelona
Ernest Giralt: Parc Científic de Barcelona
Carol V. Robinson: University of Cambridge
Christopher M. Dobson: University of Cambridge

Nature, 2005, vol. 436, issue 7050, 554-558

Abstract: Abstract Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of β-sheets oriented parallel to the fibril axis1,2. Such structures were first recognized in clinical disorders1,3, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory4,5,6,7. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains1,8. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain9,10,11,12 using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.

Date: 2005
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature03986 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:436:y:2005:i:7050:d:10.1038_nature03986

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature03986

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().