Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands

A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I) have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the str...

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Autores principales: Rosu, Silvana Antonia, Rimoldi, Omar Jorge, Prieto, Eduardo Daniel, Curto, Lucrecia M., Delfino, José M., Ramella, Nahuel Alberto, Tricerri, María Alejandra
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Ciencias Médicas
Apolipoprotein A-I
Lipoproteins
HDL particles
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/86136
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-86136
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Apolipoprotein A-I
Lipoproteins
HDL particles
spellingShingle Ciencias Médicas
Apolipoprotein A-I
Lipoproteins
HDL particles
Rosu, Silvana Antonia
Rimoldi, Omar Jorge
Prieto, Eduardo Daniel
Curto, Lucrecia M.
Delfino, José M.
Ramella, Nahuel Alberto
Tricerri, María Alejandra
Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
topic_facet Ciencias Médicas
Apolipoprotein A-I
Lipoproteins
HDL particles
description A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I) have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.
format Articulo
Articulo
author Rosu, Silvana Antonia
Rimoldi, Omar Jorge
Prieto, Eduardo Daniel
Curto, Lucrecia M.
Delfino, José M.
Ramella, Nahuel Alberto
Tricerri, María Alejandra
author_facet Rosu, Silvana Antonia
Rimoldi, Omar Jorge
Prieto, Eduardo Daniel
Curto, Lucrecia M.
Delfino, José M.
Ramella, Nahuel Alberto
Tricerri, María Alejandra
author_sort Rosu, Silvana Antonia
title Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
title_short Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
title_full Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
title_fullStr Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
title_full_unstemmed Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands
title_sort amyloidogenic propensity of a natural variant of human apolipoprotein a-i: stability and interaction with ligands
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/86136
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