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The Pharmaceutical Society of Korea (대한약학회)
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Immunoglobulin Can Be Functionally Regulated by Protein Carboxylmethylation in Fc Region

  • Park Jong-Sun (Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University, Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Cho Jae-Youl (School of Biotechnology and Bioengineering, Kangwon National University) ;
  • Kim Sung-Soo (Department of Anatomy, Ajou University School of Medicine) ;
  • Bae Hyun-Jin (Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University) ;
  • Han Jeung-Whan (Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee Hyang-Woo (Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University) ;
  • Hong Sung-Youl (Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University)
  • Published : 2006.05.01
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Abstract

Protein carboxylmethylation methylates the free carboxyl groups in various substrate proteins by protein carboxyl O-methyltransferase (PCMT) and is one of the post-translational modifications. There have been many studies on protein carboxylmethylation. However, the precise functional role in mammalian systems is unclear. In this study, immunoglobulin, a specific form of $\gamma-globulin$, which is a well-known substrate for PCMT, was chosen to investigate the regulatory roles of protein carboxylmethylation in the immune system. It was found that the anti-BSA antibody could be carboxylmethylated via spleen PCMT to a level similar to $\gamma-globulin$. This carboxylmethylation increased the hydrophobicity of the anti-BSA antibody up to 11.4%, and enhanced the antigen-binding activity of this antibody up to 24.6%. In particular, the Fc region showed a higher methyl accepting capacity with 80% of the whole structure level. According to the amino acid sequence alignment, indeed, 7 aspartic acids and 5 glutamic acids, as potential carboxylmethylation sites, were found to be conserved in the Fc portion in the human, mouse and rabbit. The carboxylmethylation of the anti-BSA antibody was reversibly demethylated under a higher pH and long incubation time. Therefore, these results suggest that protein carboxylmethylation may reversibly regulate the antibody-mediated immunological events via the Fc region.

Keywords

References

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