CONICET | Buscador de Institutos y Recursos Humanos

The sterol carrier protein 2 (SCP2) is a nonspecific lipid transfer protein that has been implicated in the transfer, uptake, and metabolism of cholesterol, branched-chain fatty acids, acyl-CoA conjugates, and other lipids. SCP2 are present as domains of multidomain proteins or as single domain polypeptides in all forms of life. SCP2 structure and function has been studied mostly in mammals and next in insects. In these organisms, it has been generally found that the main function of this protein is in the peroxysomal degradation of lipids. Very little is known about the function of this protein in plants, yeast and microorganisms. Intriguingly, Saccharomyces cerevisiae and S. Pombe are the only fungi known to lack SCP2 or any similar domain. We have previously shown that Y. lipolytica SCP2 (YLSCP2) is a 128-amino-acid basic protein inducible by fatty acids, that it is located in the yeast peroxisomes and able to bind a variety of lipids and transfer them to membranes by a collision-mediated mechanism. YLSCP2 structure was recently resolved in our lab. X-ray diffraction of the protein shows the lipid binding site as a large system of interconnected tunnels and surface pockets partially occupied by palmitate. It is evident that the cavity may accommodate larger and/or wider ligands. In order to evaluate this hypothesis, we studied the binding of YLSCP2 to lipids of different size and properties. We also measured the consumption of different lipids as a sole source of carbon, by Y. lipolytica and S. cerevisiae. A model for the binding of different lipidic ligands was developed and a working hypothesis for the function of yeast SCP2 is presented.