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

Tissue factor is the membrane-associated protein which mediates activation of factors IX and X by factor VII. In a purified, reconstituted bovine system, factor X activation by the tissue factor-factor VIIa complex is inhibited by the mixed apoproteins from human high density lipoprotein (HDL) and by isolated apolipo-protein A-II (apo A-II). Other proteins found associated with plasma lipoproteins, apolipoprotein A-I (apo A-I), C-reactive protein (CRP), and beta 2-glycoprotein I (beta 2 GPI), have been examined for effects on the activation of factor X by tissue factor-factor VIIa. In these experiments, bovine tissue factor, reconstituted into phosphatidylserine-phosphatidylcholine (PS/PC; 30/70) vesicles, was used at a single concentration while factor X (the substrate), factor VIIa (the enzyme), and the potentially inhibitory proteins were varied in a continuous chromogenic assay. Apo A-II and CRP clearly inhibit tissue factor-factor VIIa activation of factor X, while apo A-I and beta 2 GPI have little or no effect. These results demonstrate that different lipid binding proteins vary in their effects on tissue factor activity.
 ...
PMID:Effects of lipid-binding proteins apo A-I, apo A-IL, beta 2-glycoprotein I, and C-reactive protein on activation of factor X by tissue factor--factor VIIa. 313 84

Different proteins, even without sequence similarity, still can contain similar surface regions involved in protein-protein interactions with common target. These regions can serve as structural determinants of cross-reactivity and molecular mimicry. Molecular mimicry, defined as the process in which structural properties of one molecule are simulated by the dissimilar molecules, is implicated in several biologically important processes, including autoimmune and allergic reactions, binding of some ligands to common receptor, and interactions in cell signaling. The problem of identification of the determinants of molecular mimicry is not completely solved at this time. We hypothesize that identification of structurally and chemically similar surface regions of two protein molecules capable of binding to the same target will allow us to identify sites involved in cross-reactivity including determinants of the molecular mimicry. We used a graph-theoretical approach in order to determine highly similar surface regions of two proteins with known three-dimensional structures. This approach uses a variation of Maximal Common Subgraph (MCS) isomorphism, where an association graph is constructed based on the surface-exposed residues of the two molecules and the matching regions are found based on the maximum cliques in the association graph. Testing the proposed method on the targets of autoantibody involved in antiphopholipid syndrome (APS)--beta2-GPI, PC, thrombin, factor IX, factor X, and plasmin allowed identifying potential epitopes for antibody that can inhibit coagulation proteases. Application of this method to the Activated Protein C and factor VII Gla-domains revealed surface regions involved in EPCR and plasma membrane binding, consistent with known experimental results. Analysis of major pollen allergen that can cause food allergies through cross-reactivity found known epitopes involved in cross-reactivity and also revealed additional surface regions that can complement the list of epitopes. Taken together, our results suggest that the proposed graph-theoretical approach can identify determinants of cross-reactivity and molecular mimicry.
 ...
PMID:Graph-theoretical comparison of protein surfaces reveals potential determinants of cross-reactivity and the molecular mimicry. 1993 50

Lupus anticoagulants (LACs) are associated with thromboembolic complications (TECs). LACs can be detected by their anticoagulant properties in thrombin generation assays, by the peak height (PH) and lag time (LT). To assess the thrombotic risk in LAC-positive patients, we have expressed the LAC activity quantitatively by PH/LT calibration curves, constructed for mixtures of monoclonal antibodies against beta2-glycoprotein I (beta2GPI) and prothrombin, spiked in normal plasma. PH/LT was determined in LAC patients, with (n = 38) and without (n = 21) TECs and converted into arbitrary LAC units. LAC titers ranged from 0 to 200 AU/mL, with 5 of 59 patients being negative. In the positive LAC titer population (54 of 59), LAC and anti-beta2GPI immunoglobulin G (IgG) titers correlated with TECs, with odds ratios of 3.54 (95% CI, 1.0-1.7) and 10.0 (95% CI, 1.98-50.6), respectively. In patients with single or combined low titers, useful predictions on thrombosis could be made only after additional measurements of soluble P-selectin and factor VII. This layered strategy yielded positive and negative predictive values, sensitivity, and specificity values approximately 90% in this subgroup. Hence, LAC and anti-beta2GPI IgG titers, when combined with selected markers of the hypercoagulable state, allow a relevant thrombotic risk assessment in nearly all patients with LACs.
 ...
PMID:Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. 1996 29