Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure

Human beta(2)-glycoprotein I is a heavily glycosylated five-domain plasma m embrane-adhesion protein, which has been implicated in blood coagulation an d clearance of apoptotic bodies from the circulation. It is also the key an tigen in the autoimmune disease anti-phospholipid syndrome. The crystal str ucture of beta(2)-glycoprotein I isolated from human plasma reveals an elon gated fishhook-like arrangement of the globular short consensus repeat doma ins. Half of the C-terminal fifth domain deviates strongly from the standar d fold, as observed in domains one to four. This aberrant half forms a spec ific phospholipid-binding site. A large patch of 14 positively charged resi dues provides electrostatic interactions with anionic phospholipid headgrou ps and an exposed membrane-insertion loop yields specificity for lipid laye rs. The observed spatial arrangement of the five domains suggests a functio nal partitioning of protein adhesion and membrane adhesion over the Nand C- terminal domains, respectively, separated by glycosylated bridging domains. Coordinates are in the Protein Data Bank (accession No. 1QUB).