title: Phospholipid-specific conformational changes in human prothrombin upon binding to procoagulant acidic lipid membranes.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599.
authors.forename: J R
authors.initials: JR
authors.lastname: Wu
authors.forename: B R
authors.initials: BR
authors.lastname: Lentz
mesh_terms: 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
chemical_list: D000143:Acids; D000577:Amides; D008567:Membranes, Artificial; D010446:Peptide Fragments; D010718:Phosphatidylserines; D011498:Protein Precursors; C029733:prothrombin fragment 1; D011516:Prothrombin