Fibrillar conformation of an apolipoprotein A-I variant involved in amyloidosis and atherosclerosis

GISONNO, ROMINA A.; PRIETO, EDUARDO D.; GORGOJO, JUAN P.; CURTO, LUCRECIA M.; RODRIGUEZ, M. EUGENIA; ROSÚ, SILVANA A.; GADDI, GISELA M.; FINARELLI, GABRIELA S.; CORTEZ, M. FERNANDA; SCHINELLA, GUILLERMO R.; TRICERRI, M. ALEJANDRA; RAMELLA, NAHUEL A.

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ELSEVIER SCIENCE BV

Año: 2020 vol. 1864

0304-4165

Different protein conformations may be involved in the development of clinical manifestations associated with human amyloidosis. Although a fibrillar conformation is usually the signature of damage in the tissues of patients, it is not clear whether this species is per se the cause or the consequence of the disease. Hereditary amyloidosis due to variants of apolipoprotein A-I (apoA-I) with a substitution of a single amino acid is characterized by the presence of fibrillar protein within the lesions. Thus mutations result in increased protein aggregation. Here we set up to characterize the folding of a natural variant with a mutation leading to a deletion at position 107 (apoA-I Lys107-0). Patients carrying this variant show amyloidosis and severe atherosclerosis.