Fibrillar aggregates of an amyloidogenic variant of apolipoprotein A-I. Structure and cellular reactivity

ROMINA GISONNO; EDUARDO PRIETO; LUCRESIA CURTO; JUAN GORGOJO; MARIA EUGENIA RODRIGUEZ; GUILLERMO SCHINELLA; MARIA ALEJANDRA TRICERRI; NAHUEL RAMELLA

Congreso; XLVII Reunión Anual Sociedad Argentina de Biofísica.; 2018

Sociedad Argentina de Biofísica

Different protein conformations may be involved in the development of the clinical manifestations associated to human amyloidosis. Even though a fibrillar conformation is usually the signature of damage in the tissues of patients, it is not clear whether this specie is per se the cause or the consequence of the disease. Human apolipoprotein A-I (apoA-I) derived amyloidosis is poorly known. About 20 naturally occurring mutations have been described in patients suffering multiple organ failure.The reason of apoA-I variants misfolding and aggregation is far to be known. Here we set up to characterize the folding of a natural variant (apoA-I Lys107-0) which induces amyloidosis plus severe atherosclerosis. With the hypothesis that a pro-inflammatory micro environment could favor protein misfolding, we oxidized this variant under controlled amounts of H2O2. In this study, we demonstrated that the oxidation of the methionine residues of apoA-I lys 107-0 affects its conformational stability, resulting in an incorrect folding of the protein and the formation of fibrillar structures