Phosphatidylserine Regulation of Coagulation Proteins Factor IXa and Factor VIIIa

Overview

Journal J Membr Biol

Date 2022 Sep 13

PMID 36098799

Authors

Rinku Majumder

Affiliations

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Abstract

Blood coagulation is an intricate process, and it requires precise control of the activities of pro- and anticoagulant factors and sensitive signaling systems to monitor and respond to blood vessel insults. These requirements are fulfilled by phosphatidylserine, a relatively miniscule-sized lipid molecule amid the myriad of large coagulation proteins. This review limelight the role of platelet membrane phosphatidylserine (PS) in regulating a key enzymatic reaction of blood coagulation; conversion of factor X to factor Xa by the enzyme factor IXa and its cofactor factor VIIIa. PS is normally located on the inner leaflet of the resting platelet membrane but appears on the outer leaflet surface of the membrane surface after an injury happens. Human platelet activation leads to exposure of buried PS molecules on the surface of the platelet-derived membranes and the exposed PS binds to discrete and specific sites on factors IXa and VIIIa. PS binding to these sites allosterically regulates both factors IXa and VIIIa. The exposure of PS and its binding to factors IXa/VIIIa is a vital step during clotting. Insufficient exposure or a defective binding of PS to these clotting proteins is responsible for various hematologic diseases which are discussed in this review.

Citing Articles

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Chakraborty H, Sengupta D J Membr Biol. 2022; 255(6):633-635.

PMID: 36367553 DOI: 10.1007/s00232-022-00273-7.

References

Banerjee M, Drummond D, Srivastava A, Daleke D, Lentz B . Specificity of soluble phospholipid binding sites on human factor Xa. Biochemistry. 2002; 41(24):7751-62. DOI: 10.1021/bi020017p. View

Bhatnagar N, Hall G . Major bleeding disorders: diagnosis, classification, management and recent developments in haemophilia. Arch Dis Child. 2017; 103(5):509-513. DOI: 10.1136/archdischild-2016-311018. View

Brummel-Ziedins K, Branda R, Butenas S, Mann K . Discordant fibrin formation in hemophilia. J Thromb Haemost. 2009; 7(5):825-32. PMC: 3400970. DOI: 10.1111/j.1538-7836.2009.03306.x. View

Croteau S, Frelinger 3rd A, Gerrits A, Michelson A . Decreased platelet surface phosphatidylserine predicts increased bleeding in patients with severe factor VIII deficiency. J Thromb Haemost. 2020; 19(4):976-982. DOI: 10.1111/jth.15223. View

Davie E, Fujikawa K, Kisiel W . The coagulation cascade: initiation, maintenance, and regulation. Biochemistry. 1991; 30(43):10363-70. DOI: 10.1021/bi00107a001. View

Fay P, Haidaris P, Smudzin T . Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit. J Biol Chem. 1991; 266(14):8957-62. View

Furie B, Bouchard B, Furie B . Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood. 1999; 93(6):1798-808. View

Gilbert G, Arena A . Phosphatidylethanolamine induces high affinity binding sites for factor VIII on membranes containing phosphatidyl-L-serine. J Biol Chem. 1995; 270(31):18500-5. DOI: 10.1074/jbc.270.31.18500. View

Gilbert G, Arena A . Activation of the factor VIIIa-factor IXa enzyme complex of blood coagulation by membranes containing phosphatidyl-L-serine. J Biol Chem. 1996; 271(19):11120-5. DOI: 10.1074/jbc.271.19.11120. View

10.

Gilbert G, Drinkwater D . Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine. Biochemistry. 1993; 32(37):9577-85. DOI: 10.1021/bi00088a009. View

11.

Gilbert G, Furie B, Furie B . Binding of human factor VIII to phospholipid vesicles. J Biol Chem. 1990; 265(2):815-22. View

12.

Griffith M, Reisner H, Lundblad R, Roberts H . Measurement of human factor IXa activity in an isolated factor X activation system. Thromb Res. 1982; 27(3):289-301. DOI: 10.1016/0049-3848(82)90076-7. View

13.

Haque , Das , Moulik . Mixed Micelles of Sodium Deoxycholate and Polyoxyethylene Sorbitan Monooleate (Tween 80). J Colloid Interface Sci. 1999; 217(1):1-7. DOI: 10.1006/jcis.1999.6267. View

14.

Hrachovinova I, Cambien B, Hafezi-Moghadam A, Kappelmayer J, Camphausen R, Widom A . Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med. 2003; 9(8):1020-5. DOI: 10.1038/nm899. View

15.

Jardim L, Chaves D, Silveira-Cassette A, Simoes E Silva A, Santana M, Cerqueira M . Immune status of patients with haemophilia A before exposure to factor VIII: first results from the HEMFIL study. Br J Haematol. 2017; 178(6):971-978. DOI: 10.1111/bjh.14799. View

16.

Jones M, Lentz B, Dombrose F, Sandberg H . Comparison of the abilities of synthetic and platelet-derived membranes to enhance thrombin formation. Thromb Res. 1985; 39(6):711-24. DOI: 10.1016/0049-3848(85)90255-5. View

17.

Kane W, Davie E . Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood. 1988; 71(3):539-55. View

18.

Kawano M, Nagata S . Lupus-like autoimmune disease caused by a lack of Xkr8, a caspase-dependent phospholipid scramblase. Proc Natl Acad Sci U S A. 2018; 115(9):2132-2137. PMC: 5834722. DOI: 10.1073/pnas.1720732115. View

19.

Koppaka V, Wang J, Banerjee M, Lentz B . Soluble phospholipids enhance factor Xa-catalyzed prothrombin activation in solution. Biochemistry. 1996; 35(23):7482-91. DOI: 10.1021/bi952063d. View

20.

Lawson J, Mann K . Cooperative activation of human factor IX by the human extrinsic pathway of blood coagulation. J Biol Chem. 1991; 266(17):11317-27. View