The central type y amphipathic alfa-helices of apolipoprotein A-I

GONZALEZ, M. C.; TOLEDO, J. D.; TRICERRI, A.; GARDA, H.

Montevideo, Rca. Uruguay

Congreso; 6th Internacional Conference of Biological Physics. 5th Southern cone Biophysical Congress. 34th Annual meeting of the Argentinean Biophysical Society; 2007

6th Internacional Conference of Biological Physics. 5th Southern cone Biophysical Congress. 34th Annual meeting of the Argentinean Biophysical Society

In different cells, apolipoprotein A-I (apoAI) triggers mobilization of intracellular cholesterol toward the cell membrane. Previous results indicate that central region containing two amphipathic a-helical repeats inserts into phospholipid membranes and seems to behave as a functionally independent domain. Also, a short peptide with the sequence of this apoAI region (AI 77-120) retains the full activity to promote cholesterol efflux from Chinese hamster ovary (CHO) cell cultures. Our aim was to investigate the role of this central sequence of apoAI in cellular responses involving cholesterol transport and efflux. We used AI 77-120 peptide and two apoAI variants; one of them has its central Y helix pair replaced by the C terminal one (H9-10@H3-4), the other mutant (ÄK107) has a lysine residue deleted in the central region. All these apoAI variants promote cell cholesterol efflux. Except ÄK107, all the tested variants decrease the cholesterol pool available for esterification by acyl-CoA acyl transferase (ACAT) and increase mobilization of newly synthesized cholesterol toward the cell membrane. We conclude that the central apoAI domain is responsible and sufficient for these cellular responses. Its functionality would require a type Y charge distribution in the polar helix face, as well as a correct polar/hydrophilic face orientation throughout the helices, which is disrupted in ÄK107.