Change search
ReferencesLink to record
Permanent link

Direct link
Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 7, 1999-2011 p.Article in journal (Refereed) Published
Abstract [en]

Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amyloid fibrils. The transthyretin (TTR)-related proteins comprise a protein family of 5-hydroxyisourate hydrolases with structural similarity to TTR. In this study, we tested the amyloidogenic properties, if any, of sea bream TTR (sbTTR) and Escherichia coli transthyretin-related protein (ecTRP), which share 52% and 30% sequence identity, respectively, with hTTR. We obtained filamentous structures from all three proteins under various conditions, but, interestingly, different structures displayed different tinctorial properties. hTTR and sbTTR formed thin, curved fibrils at low pH (pH 2-3) that bound thioflavin-T (thioflavin-T-positive) but did not stain with Congo Red (CR) (CR-negative). Aggregates formed at the slightly higher pH of 4.0-5.5 had different morphology, displaying predominantly amorphous structures. CR-positive material of hTTR was found in this material, in agreement with previous results. ecTRP remained soluble at pH 2-12 at ambient temperatures. By raising of the temperature, fibril formation could be induced at neutral pH in all three proteins. Most of these temperature-induced fibrils were thicker and straighter than the in vitro fibrils seen at low pH. In other words, the temperature-induced fibrils were more similar to fibrils seen in vivo. The melting temperature of ecTRP was 66.7 degrees C. This is approximately 30 degrees C lower than the melting temperatures of sbTTR and hTTR. Information from the crystal structures was used to identify possible explanations for the reduced thermostability of ecTRP.

Place, publisher, year, edition, pages
Wiley InterScience , 2009. Vol. 276, no 7, 1999-2011 p.
Keyword [en]
Amyloid, fibril formation, HIU hydrolase, transthyretin, transthyretin-related protein
URN: urn:nbn:se:umu:diva-20436DOI: 10.1111/j.1742-4658.2009.06936.xPubMedID: 19250316OAI: diva2:208702
Available from: 2009-03-19 Created: 2009-03-19 Last updated: 2012-06-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Lundberg, ErikOlofsson, AndersSauer-Eriksson, A Elisabeth
By organisation
Department of ChemistryDepartment of Medical Biochemistry and Biophysics
In the same journal
The FEBS Journal

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: 72 hits
ReferencesLink to record
Permanent link

Direct link