Summary
This paper provides evidence to demonstrate that human prothrombin undergoes conformational
changes upon binding to procoagulant membranes specifically containing phosphatidylserine
(PS). Fourier transform infrared spectroscopy was used to show a slight increase in
ordered (α-helix, β-sheet, β-turns) secondary structure upon binding to PS-containing
membranes. Thermograms representing prothrombin and prothrombin fragment 1 denaturation
were obtained using differential scanning calorimetry. These were analyzed and interpreted
in terms of changes in prothrombin domain organization associated with binding to
PS-containing membranes. Changes in either secondary structure or domain organization
upon binding to negatively-charged phosphatidylglycerol-containing membranes were,
if they occurred at all, much less dramatic. The results paralleled results obtained
previously with bovine prothrombin (1, 2). The implications of these results in terms
of a possible molecular mechanism for the cofactor-like role of platelet membrane
vesicles in prothrombin activation are discussed.
