Apolipoprotein H
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
β2-glycoprotein 1, also known as beta-2 glycoprotein 1 and Apolipoprotein H (Apo-H), is a 38 kDa multifunctional plasma protein that in humans is encoded by the APOH gene.[5] One of its functions is to bind cardiolipin. When bound, the structure of cardiolipin and β2-GP1 both undergo large changes in structure.[6] Within the structure of Apo-H is a stretch of positively charged amino acids (protein sequence positions 282-287), Lys-Asn-Lys-Glu-Lys-Lys, which are involved in phospholipid binding (see image on right).[7]
β2-GP1 has a complex involvement in agglutination. It appears to alter adenosine diphosphate (ADP)-mediated agglutination of platelets.[8] Normally, β2-GP1 assumes an anticoagulation activity in serum (by inhibiting coagulation factors); 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.[9]
Inhibitory activities
β2-GP1 appears to completely inhibit serotonin release by the platelets[10] and prevents subsequent waves of the ADP-induced aggregation. The activity of β2-GP1 appears to involve the binding of negatively charged compounds, occluding the negative charges from binding and activating factor XIIa (Hageman Factor), thus inhibiting agglutination by contact activation of the intrinsic blood coagulation pathway.[11][12] Additionally, β2-GP1 causes a reduction of the prothrombinase complex binding sites on platelets and additionally 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.[13]
β2-GP1 also inhibits the generation of factor Xa in the presence of platelets.[14]
In addition, β2-GP1 inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles[15] 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.[16] This inhibitory activity is diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.[17] This indicates that under certain conditions Apo-H takes on procoagulation properties.
Pathology
Anti-β2-GP1 antibodies are found in both infectious and some systemic autoimmune diseases (eg. systemic lupus erythematosus (SLE)).[18] Positivity for anti-cardiolipin antibodies in diagnostic tests for autoimmune antiphospholipid syndrome requires the presence of β2-GP1in the cardiolipin extract.[19][20] Anti-β2-GP1 antibodies are strongly associated with thrombotic forms of lupus.
Sushi 2 protein domain
In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2 glycoprotein 1 (β2-GP1). 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.[21]
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.[22] 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.[21]
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.[22] Development of antibodies against β2-GP1 can lead to Antiphospholipid syndrome which often leads to pregnancy complications.[21]