Structure-based analysis of A19D, a variant of transthyretin involved in familial amyloid cardiomyopathy.

ABSTRACT: Transthyretin (TTR) is a tetrameric beta-sheet-rich protein. Its deposits have been implicated in four different amyloid diseases. Although aggregation of the wild-type sequence is responsible for the senile form of the disease, more than one hundred variants have been described thus far, most of which confer a more amyloidogenic character to TTR, mainly because they compromise the stability of the protein in relation to monomer formation, which upon misfolding is intrinsically aggregation-prone. We report the case of a Brazilian patient suffering from a severe cardiomyopathy who carries a rare mutation in exon 2 of the TTR gene that results in an Ala to Asp substitution at position 19 (A19D). The putative pathogenic mechanisms of this variant were analyzed in silico. We constructed a stru

SUBMITTER: Ferreira P 

PROVIDER: S-EPMC3866121 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature