ArticleJournal of molecular biology2013
Structural and functional studies of γ-carboxyglutamic acid domains of factor VIIa and activated Protein C: role of magnesium at physiological calcium.
Article in Journal of molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Structure of factor VII Gla domain bound to EPCR.Blood advances · 2026Article
- Enhancing Tissue Factor Production: The Role of N-Glycosylation and ERAD Pathway Modulation.Protein and peptide letters · 2025Article
- Identification of a broad lipid repertoire associated to the endothelial cell protein C receptor (EPCR).Scientific reports · 2022Article
- Antioxidant/anti-inflammatory effect of MgReviews in medical virology · 2022Review
- Structure of human factor VIIa-soluble tissue factor with calcium, magnesium and rubidium.Acta crystallographica. Section D, Structural biology · 2021Article
- Reduced Plasma Magnesium Levels in Type-1 Diabetes Associate with Prothrombotic Changes in Fibrin Clotting and Fibrinolysis.Thrombosis and haemostasis · 2020Article
- Coagulatory Defects in Type-1 and Type-2 Diabetes.International journal of molecular sciences · 2019Review
- The Role of Serum Calcium Level in Intracerebral Hemorrhage Hematoma Expansion: Is There Any?Neurocritical care · 2019Review
- Sodium-site in serine protease domain of human coagulation factor IXa: evidence from the crystal structure and molecular dynamics simulations study.Journal of thrombosis and haemostasis : JTH · 2019Article
- Lipid specificity of the membrane binding domain of coagulation factor X.Journal of thrombosis and haemostasis : JTH · 2017Article
- Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients.PloS one · 2016Article
- Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.Seminars in thrombosis and hemostasis · 2015Review
- Tissue Factor Residues That Modulate Magnesium-Dependent Rate Enhancements of the Tissue Factor/Factor VIIa Complex.Biochemistry · 2015Article
- Quantifying vitamin K-dependent holoprotein compaction caused by differential γ-carboxylation using high-pressure size exclusion chromatography.Analytical biochemistry · 2015Article
- Ca2+ switches the effect of PS-containing membranes on Factor Xa from activating to inhibiting: implications for initiation of blood coagulation.The Biochemical journal · 2014Article
- Influence of membrane composition on the enhancement of factor VIIa/tissue factor activity by magnesium ions.Thrombosis and haemostasis · 2014Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Crystal structures of factor (F) VIIa/soluble tissue factor (TF), obtained under high Mg(2+) (50mM Mg(2+)/5mM Ca(2+)), have three of seven Ca(2+) sites in the γ-carboxyglutamic acid (Gla) domain replaced by Mg(2+) at positions 1, 4, and 7. We now report structures under low Mg(2+) (2.5mM Mg(2+)/5mM Ca(2+)) as well as under high Ca(2+) (5mM Mg(2+)/45 mM Ca(2+)). Under low Mg(2+), four Ca(2+) and three Mg(2+) occupy the same positions as in high-Mg(2+) structures. Conversely, under low Mg(2+), reexamination of the structure of Gla domain of activated Protein C (APC) complexed with soluble endothelial Protein C receptor (sEPCR) has position 4 occupied by Ca(2+) and positions 1 and 7 by Mg(2+). Nonetheless, in direct binding experiments, Mg(2+) replaced three Ca(2+) sites in the unliganded Protein C or APC. Further, the high-Ca(2+) condition was necessary to replace Mg4 in the FVIIa/soluble TF structure. In biological studies, Mg(2+) enhanced phospholipid binding to FVIIa and APC at physiological Ca(2+). Additionally, Mg(2+) potentiated phospholipid-dependent activations of FIX and FX by FVIIa/TF and inactivation of activated factor V by APC. Since APC and FVIIa bind to sEPCR involving similar interactions, we conclude that under the low-Mg(2+) condition, sEPCR binding to APC-Gla (or FVIIa-Gla) replaces Mg4 by Ca4 with an attendant conformational change in the Gla domain ω-loop. Moreover, since phospholipid and sEPCR bind to FVIIa or APC via the ω-loop, we predict that phospholipid binding also induces the functional Ca4 conformation in this loop. Cumulatively, the data illustrate that Mg(2+) and Ca(2+) act in concert to promote coagulation and anticoagulation.
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