vitamin-k-semiquinone-radical and lysophosphatidylserine

In a calcium-dependent interaction critical for blood coagulation, vitamin K-dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via gamma-carboxyglutamic acid-rich (Gla) domains. Gla domain-mediated protein-membrane interaction is required for generation of thrombin, the terminal enzyme in the coagulation cascade, on a physiologic time scale. We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain. The serine head group binds Gla domain-bound calcium ions and Gla residues 17 and 21, fixed elements of the Gla domain fold, predicting the structural basis for phosphatidylserine specificity among Gla domains. Gla domains provide a unique mechanism for protein-phospholipid membrane interaction. Increasingly Gla domains are being identified in proteins unrelated to blood coagulation. Thus, this membrane-binding mechanism may be important in other physiologic processes.

Topics: 1-Carboxyglutamic Acid; Amino Acid Sequence; Animals; Arginine; Binding Sites; Blood Coagulation; Calcium; Cattle; Cell Membrane; Crystallography, X-Ray; Ions; Lysophospholipids; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Peptides; Protein Binding; Protein Structure, Tertiary; Prothrombin; Vitamin K