Folding of a natural variant of human apolipoprotein A-I associated with aterosclerosis microenvironment and function?.

GIOSONNO ROMINA; DIAZ LUDOVICO IVO; TRICERRI, M. A; RAMELLA NAHUEL; GARDA, H. A.; GONZALEZ MARINA CECILIA

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica SAB

Human apolipoprotein A-I, the major protein frac􀀁on of the High density lipoproteins (HDL) has long been considered a protec􀀁ve factor against the development of coronary heart disease. However, it has been isolated in large propor􀀁on from atheromatous plaques such as lipid-free, oxidized, proteolyzed and crosslinked, and the ex vivo oxida􀀁on of this protein or HDL impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase ac􀀁vi􀀁es of the lipoprotein. Likewise, the dele􀀁on of a residue (Lys 107)resulted in the deposi􀀁on of the protein within atherosclerosis plaques and associated to amyloid deposits.The presence of protein aggregates in this landscape may suggest that a shi􀀃 from the na􀀁ve conformation should result in a loss of func􀀁on. To elucidate whether structural changes may be responsible for the protein deposi􀀁on and misfunc􀀁on, we compared by biophysical approaches the dele􀀁on mutant Lys107-0 structure with respect to the protein with the na􀀁ve sequence (Wt), either freshly resuspended or a􀀃er controlled oxida􀀁on and crosslinked protein.