Lipid-protein interaction of a natural variant of apolipoprotein A-I. Studies with monolayer and bilayer models.

IVO DÍAZ LUDOVICO; ROMINA VAZQUEZ; SABINA MATE; MARÍA ALEJANDRA TRICERRI; HORACIO ALBERTO GARDA; MARINA CECILIA GONZALEZ

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. XLVI Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2017

SAIC, SAIB, SAI, SAA, SAB, SAB (biología), SAFE, SAFIS, SAH, SAP

Human apolipoprotein A-I (ApoA-I) is the major protein component of high density lipoproteins (HDL) serving as transporters for excess of cellular cholesterol (C) through the plasma compartment to the liver. Several single amino acid replacement natural ApoA-I variants have been described in which protein´s function is impaired, resulting in chronic pathologies such as atherosclerosis or amyloidosis. One of this mutant having a deletion of the single residue Lys107 (∆K107) induces severe atherosclerosis. We have investigated by biophysical approaches the bilayer´s or monolayer´s interaction of this mutant in comparison with the protein with the wild sequence (Wt). In order to compare the ability to interact with both layers, we have measured the leakage induction of POPC and POPC:C (4:1) vesicles loaded with terbium/dipicolinic acid, as well as the interaction with POPC and POPC:C (4:1) monolayers by surface tension measures in a Langmuir balance. Both proteins induce a rapid leakage of the POPC or POPC:C vesicles. Nevertheless, the induced leakage for both proteins is higher with POPC:C liposomes than with POPC vesicles. In monolayers, the differences of surface tension were higher for the Wt (∆Π~14,0mN/m) than for the ∆K107 (∆Π~8,5mN/m) protein with POPC monolayers at Π0=10mN/m. However, this effect is not observed in POPC:C monolayers (for both Wt and ∆K107; ∆Π~9,0mN/m) at Π0=10mN/m. These results suggest that the interaction of the protein with POPC or POPC:C bilayers are not affected by the deletion. With low Π0 monolayers, however, Wt protein is most effcient than ∆K107 to increase the surface tension in POPC monolayers.