Molecular dynamics study of the structural characteristics of apoA-1 in double belt LL5 / 2 conformation

LYNN S; MONGI S; PRIETO ED; MCCARTHY A; GARDA HA

Santiago del Estero

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2015

Sociedad Argentina de Biofísica (SAB)

Apolipoprotein A1 (apoA-1) is one of the major proteinspresent in the high density lipoprotein particles  (HDL) that are involved in reversecholesterol transport and play a key role in the removal excess of thismolecule. HDL particles transported cholesterol (CHOL) from the tissues to theliver where it is metabolized and eliminated (1). ApoA-1 is an amphipathicprotein, which performs its function through a series of conformational changesthat include sole protein conformation, membrane bound protein and discoidaland spherical HDL particles, with different compositions and sizes (Prieto,2011). In this paper we present a molecular dynamics study of the structuralcharacteristics of an HDL particlecomprised of two chains of apoA-1 in double belt LL5 / 2 conformation (3),containing a bilayer of 161 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), ascompared to the reference LL5 / 5 model particle proposed by Segrest (1999).References1-     RAMELLA, Nahuel A., et al. Human apolipoprotein AI naturalvariants: molecular mechanisms underlying amyloidogenic propensity. PloS one, 2012, vol. 7, no 8, p. e43755.2-     PRIETO, Eduardo D.; GARDA, Horacio A. Membraneinsertion topology of the central apolipoprotein AI region. Fluorescencestudies using single tryptophan mutants. Biochemistry, 2010, vol. 50, no 4, p. 466-479.3-     SILVA, RA Gangani D., et al. A massspectrometric determination of the conformation of dimeric apolipoprotein AI indiscoidal high density lipoproteins.Biochemistry,2005, vol. 44, no 24, p. 8600-8607.4-     SEGREST, Jere P., et al. A detailed molecularbelt model for apolipoprotein AI in discoidal high density lipoprotein. Journal of Biological Chemistry, 1999,vol. 274, no 45, p. 31755-31758.