STRUCTURE OF MEMBRANE-BOUND HUMAN FACTOR VA

Coagulation factor Va is an essential cofactor which combines with the serine protease factor Xa on a phospholipid surface to form the proth rombinase complex. In the present study, the structure of factor Va in teracting with lipid surfaces containing phosphatidylserine was studie d by electron microscopy. Two-dimensional crystals of factor Va were o btained on planar lipid films under quasi-physiological conditions. Th e two-dimensional projected structure of factor Va was calculated at a resolution of 2 nm, revealing dimers of factor Va arranged on the sur face lattice with the symmetry of the plane group p2. Average unit cel l dimensions are a = 14.4 nm, b = 8.8 nm, gamma = 107 degrees. Each fa ctor Va molecule presents two distinct domains of protein density cons isting of one small domain, of 3 nm in diameter, connected to a larger domain of about 6 nm x 4.5 nm. The projected structure of factor Va c overs an area equivalent to about fifty phospholipid molecules. In add ition, edge-on views of factor Va molecules bound to liposomes reveal a globular structure connected through a thin stem to the liposome sur face. A three-dimensional model of membrane-bound factor Va is propose d.