Publication Abstract from PubMed
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.
Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.,Huang M, Rigby AC, Morelli X, Grant MA, Huang G, Furie B, Seaton B, Furie BC Nat Struct Biol. 2003 Sep;10(9):751-6. Epub 2003 Aug 17. PMID:12923575[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
