β2-glycoprotein 1, also known as beta-2 glycoprotein 1 and Apolipoprotein H, is a 38 kDa multifunctional plasma protein that in humans is encoded by the APOH gene. One of its functions is to bind cardiolipin. When bound, the structure of cardiolipin and β2-GP1 both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively chargedamino acids, Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipidbinding. β2-GP1 has a complex involvement in agglutination. It appears to alter adenosine diphosphate -mediated agglutination of platelets. Normally, β2-GP1 assumes an anticoagulation activity in serum ; however, changes in blood factors can result in a reversal of that activity. Although previously referred to as apolipoprotein H, it is not present in appreciable quantities in the lipoprotein fractions, so ApoH is therefore thought to be a misnomer.
Inhibitory activities
β2-GP1 appears to completely inhibit serotonin release by the platelets and prevents subsequent waves of the ADP-induced aggregation. The activity of β2-GP1 appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway. β2-GP1 causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of β2-GP1 suggesting a regulatory role of β2-GP1 in coagulation. β2-GP1 also inhibits the generation of factor Xa in the presence of platelets. β2-GP1 also inhibits that activation of factor XIIa. In addition, β2-GP1 inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va. This inhibitory activity is diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive. This indicates that under certain conditions Apo-H takes on procoagulation properties.
In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2 glycoprotein 1. This protein domain is only found in eukaryotes. The first four domains found in Apolipoprotein H resemble each other, however the fifth one appears to be different.
Structure
This protein domain is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. Additionally, the fifth protein domain appears to resemble the other four in Apolipoprotein with the exception of three internal disulfide bonds and an extra C-terminal loop.
Function
Its exact function remains to be fully elucidated; however it is known to play an important role in the binding of β2-GP1 to negatively charged compounds and subsequent capture for binding of anti-β2-GP1 antibodies. Development of antibodies against β2-GP1 can lead to Antiphospholipid syndrome which often leads to pregnancy complications.
