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)

The horseshoe crab clotting factor, factor C, present in the hemocytes is a serine-protease zymogen activated with lipopolysaccharide. It is a two-chain glycoprotein (Mr = 123,000) composed of a heavy chain (Mr = 80,000) and a light chain (Mr = 43,000) [T. Nakamura et al. (1986) Eur. J. Biochem. 154, 511-521]. In our continued study of this zymogen, we have now also found a single-chain form of factor C (Mr = 123,000) in the hemocyte lysate. The heavy chain had the NH2-terminal sequence of Ser-Gly-Val-Asp-, consistent with that of the single-chain factor C, indicating that the heavy chain is derived from the NH2-terminal part of the molecule. The light chain had an NH2-terminal sequence of Ser-Ser-Gln-Pro-. Incubation of the two-chain zymogen with lipopolysaccharide resulted in the cleavage of a Phe-Ile bond between residues 72 and 73 of the light chain. Concomitant with this cleavage, the A (72 amino acid residues) and B chains derived from the light chain were formed. The complete amino acid sequence of the A chain was determined by automated Edman degradation. The A chain contained a typical segment which is similar in sequence to a family of repeats in human beta 2-glycoprotein I, complement factors B, protein H, C4b-binding protein, and coagulation factor XIII b subunit. The NH2-terminal sequence of the B chain was Ile-Trp-Asn-Gly-. This chain contained the serine-active site sequence-Asp-Ala-Cys-Ser-Gly-Asp-Ser-Gly-Gly-Pro-. These results indicate that horseshoe crab factor C exists in the hemocytes in a single-chain zymogen form and is converted to an active serine protease by hydrolysis of a specific Phe-Ile peptide bond.
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PMID:Lipopolysaccharide-sensitive serine-protease zymogen (factor C) of horseshoe crab hemocytes. Identification and alignment of proteolytic fragments produced during the activation show that it is a novel type of serine protease. 330 57

The general hypothesis for the biological function of beta 2-glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation. In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. Activation was accomplished by an ellagic acid-phospholipid suspension (Cephotest) and measured by the appearance of amidolytic activity using the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302). This inhibitory effect of beta 2-glycoprotein I was observed both when Cephotest was preincubated with beta 2-glycoprotein I and when the amount of beta 2-glycoprotein I in plasma was increased by addition of beta 2-glycoprotein I to either normal or beta 2-glycoprotein I-deficient plasma. The inhibitory effect of beta 2-glycoprotein I on the contact phase activation could be one of the physiological functions of this protein.
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PMID:beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway. 405 28

beta2-Glycoprotein I was shown to bind reversibly to calmodulin in a Ca2+-dependent manner with a 1:1 stoichiometry, a Kd of 3 x 10(-9) M and a Hill coefficient of 1.4. A sequence in beta2-glycoprotein I (Lys-Pro-Gly-Tyr-Val-Ser-Arg-Gly-Gly-Met-Arg-Lys-Phe-Ile-) limited by Cys-32 and Cys-47 is suggested to be the calmodulin-binding region. This sequence was the only one in beta2-glycoprotein I theoretically having the ability to form a basic amphiphilic alpha-helix typical of a calmodulin binding sequence. The peptide corresponding to this sequence was synthesized and found to inhibit the interaction between beta2-glycoprotein I and calmodulin with an IC50 value of 0.38 x [beta2-glycoprotein I] and to displace the beta2-glycoprotein I from the beta2-glycoprotein I/calmodulin complex with an IC50 value of 0.90 x [beta2-glycoprotein I].
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PMID:Characterization of the interaction between beta2-glycoprotein I and calmodulin, and identification of a binding sequence in beta2-glycoprotein I. 918 41

Apolipoprotein H (apoH, protein; APOH, gene) binds to negatively charged phospholipids, which triggers the production of a subset of autoantibodies against phospholipid in patients with autoimmune diseases. We have demonstrated that two naturally occurring missense mutations in the fifth domain of apoH, Trp316Ser and Cys306Gly, disrupt the binding of native apoH to phosphatidylserine [Sanghera, D. K., Wagenknecht, D. R., McIntyre, J. A. & Kamboh, M. I. (1997) Hum. Mol. Genet. 6, 311-316]. To confirm whether these are functional mutations, we mutagenized APOH cDNAs and transiently expressed them in COS-1 cells. The cardiolipin ELISA of wild-type and mutant recombinant apoH confirmed that the Gly306 and Ser316 mutations are responsible for abolishing the binding of recombinant apoH to cardiolipin. These mutations, however, had no effect on the levels of expression or secretion of recombinant apoH in transfected COS-1 cells. While the Cys306Gly mutation disrupts a disulfide bond between Cys306 and Cys281, which appears to be critical for clustering positively charged amino acids, the Trp316Ser mutation affects the integrity of an evolutionarily conserved hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp), which is hypothesized to interact with anionic phospholipid. To test this hypothesis, we exchanged the remaining three hydrophobic amino acids with neutral amino acids by site-directed mutagenesis (Leu313Gly, Ala314Ser and Phe315Ser). Binding of the Leu313Gly and Phe315Ser mutants to cardiolipin was significantly reduced to 25% and 13%, respectively, of that of the wild-type. On the other hand, the Ala314Ser mutation showed normal cardiolipin binding. Taken together with our previous findings, these results strongly suggest that the configuration of the fifth domain of apoH, as well as the integrity of the highly conserved hydrophobic amino acids at positions 313-316, is essential for the binding of apoH to anionic phospholipid.
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PMID:A hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp) in the fifth domain of apolipoprotein H (beta2-glycoprotein I) is crucial for cardiolipin binding. 1071 9