liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Thermodynamic stability and denaturation kinetics of a benign natural transthyretin mutant identified in a Danish kindred
University of Copenhagen.
Linköping University, Department of Physics, Chemistry and Biology, Protein Science. Linköping University, Faculty of Science & Engineering.
Vejle Hospital.
Vejle Hospital.
Show others and affiliations
2011 (English)In: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, ISSN 1350-6129, Vol. 18, no 2, 35-46 p.Article in journal (Refereed) Published
Abstract [en]

The disease phenotype of transthyretin (TTR) is dramatically influenced by single point mutations in the TTR gene. Herein, we report on a novel mutation D99N (Asp99Asn) in TTR found in a Danish kindred. None of the family members carrying this mutation have so far shown any clinical signs of amyloidosis. One carrier found compound heterozygous for TTR D99N and L111M (Leu111Met) associated with cardiac amyloid is asymptomatic (42 years). Disease severity can often be linked to both the kinetics of fibril formation and the degree of destabilisation of the native state. In this study, we show that the thermodynamic stability and rate of tetramer dissociation of the variant TTR D99N is unchanged or slightly more stable than wild type (WT) TTR. Furthermore, the in vitro fibrillation kinetics of the variant reveals an unchanged or slightly suppressed tendency to form fibrils compared to WT. Thus, the in vitro experiments support the lack of clinical symptoms observed so far for the TTR D99N carriers. In line with this, studies on kinetic stability and fibrillation kinetics reveal indistinguishable stability of TTR heterotetramers D99N/L111M compared to the heterotetramers WT/L111M. In conclusion, TTR D99N is predicted to be a non-pathogenic benign mutation with WT properties.andlt;/.

Place, publisher, year, edition, pages
Informa Healthcare , 2011. Vol. 18, no 2, 35-46 p.
Keyword [en]
Amyloidosis, kinetics, mutation, stability, transthyretin
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-68695DOI: 10.3109/13506129.2011.560215ISI: 000290486500001OAI: diva2:419706
Available from: 2011-05-27 Created: 2011-05-27 Last updated: 2015-05-28

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Hammarström, Per
By organisation
Protein ScienceFaculty of Science & EngineeringBiochemistryThe Institute of Technology
Engineering and Technology

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: 50 hits
ReferencesLink to record
Permanent link

Direct link