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Immunoglobulin can be functionally regulated by protein carboxylmethylation in Fc region

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Abstract

Protein carboxylmethylation methylates the free carboxyl groups in various substrate proteins by protein carboxylO-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 γ-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 anibody could be carboxylmethylatedvia spleen PCMT to a level similar to γ-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.

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Authors and Affiliations

  1. Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University, 440-746, Suwon, Korea

    Jong Sun Park, Hyun Jin Bae & Sung Youl Hong

  2. Department of Pharmacology, College of Medicine, Chungnam National University, 301-131, Taejon, Korea

    Jong Sun Park

  3. School of Biotechnology and Bioengineering, Kangwon National University, 200-701, Chuncheon, Korea

    Jae Youl Cho

  4. Department of Anatomy, Ajou University School of Medicine, 442-749, Suwon, Korea

    Sung Soo Kim

  5. Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, 440-746, Suwon, Korea

    Jeung Whan Han & Hyang Woo Lee

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Park, J.S., Cho, J.Y., Kim, S.S. et al. Immunoglobulin can be functionally regulated by protein carboxylmethylation in Fc region. Arch Pharm Res 29, 384–393 (2006). https://doi.org/10.1007/BF02968588

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