CRYSTAL-STRUCTURE OF TRUNCATED HUMAN APOLIPOPROTEIN-A-I SUGGESTS A LIPID-BOUND CONFORMATION

The structure of truncated human apolipoprotein A-I (apo A-I), the maj or protein component of high density lipoprotein, has been determined at 4-Angstrom resolution, The crystals comprise residues 44-243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid, The molecule consists almost entirely of a pseudocontinuous, amphipathic cu-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensio ns 125 x 80 x 40 Angstrom, Four molecules in the asymmetric unit assoc iate via their hydrophobic faces to form an antiparallel four-helix bu ndle with an elliptical ring shape. Based on this structure, we propos e a model for the structure of apo A-I bound to high density lipoprote in.