Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether beta2-glycoprotein I (beta2GPI), the key antigen in the antiphospholipid syndrome, is susceptible to oxidative modifications by the hydroxyl radical (*OH) that may influence its lipid-binding and antigenic properties. The effects on human and bovine beta2GPI of *OH free radicals generated by gamma-radiolysis of water with 137Cs were studied. Radiolytic *OH caused a dose-dependent loss of tryptophan, production of dityrosine and carbonyl groups. dimerization and/or extensive aggregation of beta2GPI. It ensued a reduction in affinity binding to cardiolipin liposomes and loss of beta2GPI-dependent autoantibody binding to immobilized cardiolipin. Patient anti-beta2GPI antibodies (n = 20) segregated into two groups based on the effect in the beta2GPI-ELISA of beta2GPI pretreatment with *OH: enhancement (group A, n = 10) or suppression (group B, n = 10) of IgG binding. The avidities of group A antibodies for fluid-phase beta2GPI were low but increased in a dose-dependent manner upon beta2GPI irradiation, in relation to protein crosslinking. Distinguishing features of group B antibodies included higher avidities for fluid-phase beta2GPI that was no longer recognized after *OH treatment, and negative anticardiolipin tests suggesting epitope location near the phospholipid binding site. The *OH scavengers thiourea and mannitol efficiently protected against all above changes. Therefore, oxidative modifications of beta2GPI via *OH attack of susceptible amino acids alter phospholipid binding, and modulate recognition by autoantibodies depending on their epitope specificities. These findings may be of clinical relevance for the generation and/or reactivity of anti-beta2GPI antibodies.
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PMID:Oxidation of beta2-glycoprotein I (beta2GPI) by the hydroxyl radical alters phospholipid binding and modulates recognition by anti-beta2GPI autoantibodies. 1168 26