Phospholipid-specific conformational changes in human prothrombin upon binding to procoagulant acidic lipid membranes.
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 (alpha-helix, beta-sheet, beta-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.
Wu
J R
JR
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599.
Lentz
B R
BR
D000143:Acids; D000577:Amides / Q000737:chemistry; D000818:Animals; D002417:Cattle; D006801:Humans; D008567:Membranes, Artificial; D010446:Peptide Fragments / Q000737:chemistry; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D011498:Protein Precursors / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011516:Prothrombin / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D017550:Spectroscopy, Fourier Transform Infrared
D000143:Acids; D000577:Amides; D008567:Membranes, Artificial; D010446:Peptide Fragments; D010718:Phosphatidylserines; D011498:Protein Precursors; C029733:prothrombin fragment 1; D011516:Prothrombin