Structure and function of a central domain of human apolipoprotein A-I

GARDA HA; TOLEDO JD; TRICERRI MA; CORSICO B; PRIETO ED; GONZALEZ MC

Buenos Aires

Workshop; Colloquium for Humboldt Fellows and Awardees in Argentina; 2005

Humboldt Foundation, Germany

Apolipoprotein A-I (apoAI) plays a key role in reverse cholesterol transport, a process of antiatherogenic relevance producing the removal of cholesterol excess in peripheral tissues. In this report, studies from our laboratory on the structure and function of two central apoAI amphipathic a-helices with a particular charge distribution will be discussed. The behavior of a synthetic peptide suggests that these helices constitute a functional and structural domain with relative independence from the rest of apoAI molecule. This domain inserts preferentially into cholesterol-containing membranes where it would facilitate cholesterol desorption. Recent studies using the mentioned peptide and apoAI mutants, revealed that the central domain is also responsible for triggering the mobilization of intracellular cholesterol depots toward the cell membrane. For this, a specific sequence of the central amphipathic a-hélices would not be required, but the particular charge distribution of type “Y” amphipathic helices and a correct orientation of hydrophobic and hydrophilic helix faces would be necessary.