CRYSTAL-STRUCTURE OF THE ANNEXIN-XII HEXAMER AND IMPLICATIONS FOR BILAYER INSERTION

ANNEXINS are a family of calcium- and phospholipid-binding proteins(1, 2) implicated in a number of biological processes including membrane f usion(3) and ion channel formation(4-7). The crystal structure of the annexin XII hexamer, refined at 2.8 Angstrom resolution, forms a conca ve disk with 3-2 symmetry, about 100 Angstrom in diameter and 70 Angst rom thick with a central hydrophilic pore. Six intermolecular Ca2+ ion s are involved in hexamer formation. An additional 18 Ca2+ ions are lo cated on the perimeter of the disk, accessible only from the side of t he hexameric disk. On the basis of the hexamer structure we propose he re a new mode of protein-phospholipid bilayer interaction that is dist inct from the hydrophobic insertion of typical membrane proteins. This speculative model postulates the Ca2+-dependent insertion of the hydr ophilic annexin XII hexamer into phospholipid bilayers with local reor ientation of the bilayer phospholipids.