Change search
ReferencesLink to record
Permanent link

Direct link
Probing solvent accessibility of transthyretin amyloid by solution NMR spectroscopy.
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
Faculty of Medicine, Molecular Biology (Faculty of Medicine). (Lundgren)
Show others and affiliations
2004 (English)In: J Biol Chem, ISSN 0021-9258, Vol. 279, no 7, 5699-707 p.Article in journal (Refereed) Published
Abstract [en]

The human plasma protein transthyretin (TTR) may form fibrillar protein deposits that are associated with both inherited and idiopathic amyloidosis. The present study utilizes solution nuclear magnetic resonance spectroscopy, in combination with hydrogen/deuterium exchange, to determine residue-specific solvent protection factors within the fibrillar structure of the clinically relevant variant, TTRY114C. This novel approach suggests a fibril core comprised of the six beta-strands, A-B-E-F-G-H, which retains a native-like conformation. Strands C and D are dislocated from their native edge region and become solvent-exposed, leaving a new interface involving strands A and B open for intermolecular interactions. Our results further support a native-like intermolecular association between strands F-F' and H-H' with a prolongation of these beta-strands and, interestingly, with a possible shift in beta-strand register of the subunit assembly. This finding may explain previous observations of a monomeric intermediate preceding fibril formation. A structural model based on our results is presented.

Place, publisher, year, edition, pages
2004. Vol. 279, no 7, 5699-707 p.
Keyword [en]
Amyloid/*chemistry, Circular Dichroism, Electrophoresis; Polyacrylamide Gel, Humans, Hydrogen/chemistry, Magnetic Resonance Spectroscopy/*methods, Mass Spectrometry, Microscopy; Atomic Force, Models; Molecular, Prealbumin/*chemistry, Protein Conformation, Protein Structure; Secondary, Spectrophotometry, Temperature, Time Factors, Ultraviolet Rays
URN: urn:nbn:se:umu:diva-16485PubMedID: 14604984OAI: diva2:156158
Available from: 2007-10-03 Created: 2007-10-03 Last updated: 2011-01-12Bibliographically approved

Open Access in DiVA

No full text

Other links


Search in DiVA

By author/editor
Olofsson, AndersLundgren, Erik
By organisation
Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology)Molecular Biology (Faculty of Medicine)

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 34 hits
ReferencesLink to record
Permanent link

Direct link