CRYSTAL-STRUCTURE OF THE SACCHAROMYCES-CEREVISIAE PHOSPHATIDYLINOSITOL-TRANSFER PROTEIN

The yeast phosphatidylinositol-transfer protein (Sec14) catalyses exch ange of phosphatidylinositol and phosphatidylcholine between membrane bilayers in vitro(1,2). In vivo, Sec14 activity is essential for vesic le budding from the Golgi complex(3). Hero we report a three-dimension al structure for Sec14 at 2.5 A resolution. Sec14 consists of twelve a lpha-helices, six beta-strands, eight 3(10)-helices and has two distin ct domains. The carboxy-terminal domain forms a hydrophobic pocket whi ch, in the crystal structure, is occupied by two molecules of N-octyl- beta-D-glucopyranoside and represents the phospholipid-binding domain. This pocket is reinforced by a string motif whose disruption in a sec 14 temperature-sensitive mutant results in destabilization of the phos pholipid-binding domain. Finally, we have identified an unusual surfac e helix that may play a critical role in driving Sec14-mediated phosph olipid exchange. From this structure, we derive the first molecular cl ues into how a phosphatidylinositol-transfer protein functions.