101. Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.
- Author
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Huang, Mingdong, Rigby, Alan C, Morelli, Xavier, Grant, Marianne A, Huang, Guiqing, Furie, Bruce, Seaton, Barbara, and Furie, Barbara C
- Subjects
VITAMIN K ,PROTEINS ,BLOOD coagulation ,PROTEIN binding ,PHOSPHATIDYLSERINES ,ENZYMES - Abstract
In a calcium-dependent interaction critical for blood coagulation, vitamin K-dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via ?-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. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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