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Thermodynamic stabi...
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Groenning, MinnaUniversity of Copenhagen
(author)
Thermodynamic stability and denaturation kinetics of a benign natural transthyretin mutant identified in a Danish kindred
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-03-16
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Informa Healthcare,2011
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-68695
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68695URI
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https://doi.org/10.3109/13506129.2011.560215DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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;/.
Subject headings and genre
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Amyloidosis
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kinetics
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mutation
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stability
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transthyretin
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TECHNOLOGY
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TEKNIKVETENSKAP
Added entries (persons, corporate bodies, meetings, titles ...)
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Campos, Raul ILinköpings universitet,Proteinkemi,Tekniska fakulteten
(author)
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Fagerberg, ChristinaVejle Hospital
(author)
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Aamann Rasmussen, AndersVejle Hospital
(author)
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Eriksen, Ulrik HVejle Hospital
(author)
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Powers, Evan TScripps Research Institute
(author)
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Hammarström, PerLinköpings universitet,Biokemi,Tekniska högskolan(Swepub:liu)perha81
(author)
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University of CopenhagenProteinkemi
(creator_code:org_t)
Related titles
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In:AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS: Informa Healthcare18:2, s. 35-461350-6129
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In:Amyloid: Informa Healthcare18:2, s. 35-461744-2818
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