title: Lack of functional similarity between complement factor H and anticardiolipin cofactor, beta 2-glycoprotein I (apolipoprotein H).
abstract: Beta 2-glycoprotein I (beta 2-GPI) is a 50 kDa protein in human plasma composed of five repeating complement control protein modules thereby closely resembling complement factor H which has 20 such units. Both beta 2-GPI and factor H (150 kDa) have binding sites for negatively charged polyions. beta 2-GPI has been shown to act as a cofactor for antiphospholipid antibodies upon their binding to anionic phospholipids. In factor H the polyanion recognition site participates in the discrimination between alternative pathway activating and non-activating surfaces. In light of the structural similarity between beta 2-GPI and factor H we have examined whether beta 2-GPI has a role in the alternative complement pathway recognition process. Both activators (zymosan) and non-activators (sheep erythrocytes) of the alternative complement pathway were coated with C3b. Radiolabelled factor H was observed to recognize C3b on both surfaces, whereas beta 2-GPI bound to neither. In competition experiments beta 2-GPI could not prevent the association of 125I-H with either non-activator or activator bound C3b. Conversely, factor H could not replace beta 2-GPI as a cofactor for antiphospholipid antibodies upon their binding to anionic phospholipids. It is concluded that beta 2-GPI and factor H, despite similarities in structure, exhibit distinct, non-overlapping functions.
mesh_terms: D000818:Animals; D002474:Cell-Free System; D003179:Complement C3b / Q000378:metabolism; D017242:Complement Factor H / Q000502:physiology*; D004912:Erythrocytes; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D012756:Sheep; D013329:Structure-Activity Relationship; D015054:Zymosan; D053482:beta 2-Glycoprotein I
chemical_list: C493495:CFH protein, human; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D003179:Complement C3b; D017242:Complement Factor H; D015054:Zymosan