Human apolipoprotein A-I natural variants: Molecular mechanisms underlying amyloidogenic propensity

TRICERRI, MA; RAMELLA; NA; ROSU; SA; GADDI, GM; FINARELLI; GS; SCHINELLA, G; PRIETO; ED

uppsala

Simposio; XV International Symposium on Amyloidosis; 2016

ISA

Naturally occurring mutations of Human apolipoprotein A-I (apoA-I) have been shown to induce amyloidosis in patients, with a broad range of clinical manifestations, depending on the protein variant which is involved. Although the molecular mechanisms of apoA-I amyloid associated pathology remain largely unknown, the fact that the wild-type (Wt) deposits in atherosclerotic plaques supports the hypothesis that a chronic inflammatory micro environment could elicit protein aggregation In order to get insight into the mechanisms inducing apoA-I misfolding, we examined the effects of point mutations in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands.