Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1).
beta 2-GP1 is a serum protein which influences binding of anticardiolipin antibodies to cardiolipin, may influence induction of these antibodies in animals and may play a role in anticardiolipin-mediated thrombosis. Various investigators have proposed that when beta 2-GP1 binds cardiolipin, structural alterations occur in one or both molecules, resulting in exposure of new epitopes for anticardiolipin binding, but there has been no proof that such alterations occur. Utilizing Fourier transform infrared spectroscopy, this study analysed the structure of cardiolipin and beta 2-GP1 alone, then mixed with each other. For pure cardiolipin, analysis of the CH2 stretching, scissoring and carbonyl bands suggested this molecule assumes a hexagonal crystal lattice packing structure in both anhydrous and aqueous samples. Based on the second derivative analysis of the amide 1 band from the beta 2-GP1 protein backbone, as well as Fourier self-deconvolution and curve fit algorithms, beta 2-GP1 was calculated to contain 18% turns, 37% alpha-helix, and 45% beta-sheet structure. beta 2-GP1 binding with cardiolipin results in a significant change in the conformation as well as geometry of the lipid and protein components. This is indicated by a broadening of the CH stretching band and a marked shift in intensity of the carbonyl band of cardiolipin, indicating less hydrogen bonding. There was a decrease in beta-sheet structure of beta 2-GP1 from 46% to 23% and appearance of 26% to 28% random structure. These findings indicate that mixing beta 2-GP1 with cardiolipin results in profound changes in both molecules which might explain the effect of beta 2-GP1 on anticardiolipin binding activity.
Borchman
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Department of Ophthalmology and Visual Science, Kentucky Lions Eye Research Institute, University of Louisville 40292, USA.
Harris
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EN
Pierangeli
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Lamba
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D000577:Amides / Q000737:chemistry; D002308:Cardiolipins / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D053482:beta 2-Glycoprotein I
D000577:Amides; D002308:Cardiolipins; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I