Biological significance and characteristics of PIVKA-II (IMAGE)
Caption
PIVKA-II, protein induced by vitamin K absence or antagonist-II.
PIVKA-II, also known as des-γ-carboxy prothrombin (DCP), is an aberrant isoform of prothrombin characterized by defective γ-carboxylation within its Gla domain. In physiologically active prothrombin, the Gla domain contains ten fully carboxylated glutamic acid residues, which enable the protein to bind calcium ions and interact with phospholipid membranes. This is an essential step for anchoring prothrombin to the surface of injured blood vessels. In contrast, PIVKA-II contains incompletely carboxylated Gla residues, resulting in markedly reduced calcium-binding capacity and a failure to adopt the functional conformation required for coagulation activity.Site-directed mutagenesis studies have demonstrated that carboxylation at positions 16, 26, and 29 is critical for maintaining procoagulant function. Loss of γ-carboxylation at these key sites reduces the coagulation activity of PIVKA-II to less than 1% of that of native prothrombin. Moreover, structural analyses have revealed that the conformational flexibility of the Gla domain in PIVKA-II is significantly diminished, which disrupts the spatial organization of the kringle and protease domains and further compromises its biological function.
Credit
Liaoyun Zhang
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