Structural and functional properties of a central domain of human apolipoprotein A-I

GARDA H A

Rosario

Simposio; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular. Simposio sobre "Lipidos"; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

S-01 STRUCTURAL AND FUNCTIONAL PROPERTIES OF A CENTRAL DOMAIN OF HUMAN APOLIPOPROTEIN A-I Garda, H. A. Instituto de Investigaciones Bioqu¨ªmicas de La Plata (CONICETUNLP) Calles 60 y 120. 1900-La Plata E-mail: hgarda@atlas.med.unlp.edu.ar Apolipoprotein A-I (apoAI) plays a key role in several steps of reverse cholesterol transport, a process of antiatherogenic relevance that removes cholesterol excess of peripheral tissues. ApoAI is constituted almost exclusively by amphipathic ¦Á-helices and undergoes large conformational changes to exchange among lipid-free and different lipid-bound states during its functional cycle. Identification of domains involved in the different apoAI functions, and knowing the characteristics that make them critical for its activity, would provide valuable information on the mechanism of cellular lipid efflux mediated by this protein. I will focus here on a central pair of ¦Á-helices having a particular charge distribution in their polar face. 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 facilitates cholesterol desorption. Recent studies revealed that the central domain is also responsible for triggering mobilization of intracellular cholesterol depots toward the cell membrane. For its activity, a specific sequence is not required, but the charge distribution of class ¡°Y¡± amphipathic ¦Á-helices and an adequate orientation of the hydrophobic and hydrophilic helix faces would be necessary