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

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

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

Humanapolipoprotein A-I (ApoA-I) is the major protein component of high densitylipoproteins (HDL) serving as transporters for excess of cellular cholesterol(C) through the plasma compartment to the liver. Several single amino acidreplacement natural ApoA-I variants have been described in which protein´sfunction is impaired, resulting in chronic pathologies such as atherosclerosisor amyloidosis. One of this mutant having a deletion of the single residueLys107(∆K107) induces severe atherosclerosis. We have investigated by biophysicalapproaches the bilayer´s or monolayer´s interaction of this mutant incomparison with the protein with the wild sequence (Wt). In order to comparethe ability to interact with both layers, we have measured the leakageinduction of POPC and POPC:C (4:1) vesicles loaded with terbium/dipicolinicacid, as well as the interaction with POPC and POPC:C (4:1) monolayers bysurface tension measures in a Langmuir balance. Both proteins induce a rapidleakage of the POPC or POPC:C vesicles. Nevertheless, the induced leakage forboth proteins is higher with POPC:C liposomes than with POPC vesicles. Inmonolayers, 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 ofthe protein with POPC or POPC:C bilayers are not affected by the deletion. Withlow Π0 monolayers, however, Wt protein is most effcient than ∆K107 to increasethe surface tension in POPC monolayers.Keywords: apolipoprotein A-I; deletion mutant; leakage; vesicles; monolayer.