Cysteine Residues Required for the Attachment of the Light Chain in Human IgA2
| Autor: | Koteswara R. Chintalacharuvu, Kunihiko Kobayashi, Sherie L. Morrison, Nishant Bhola, Li J. Yu, Christine Z. Fernandez |
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| Rok vydání: | 2002 |
| Předmět: |
Protein Folding
Stereochemistry Molecular Sequence Data Immunology Transfection Immunoglobulin light chain Mice chemistry.chemical_compound fluids and secretions stomatognathic system Tumor Cells Cultured Disulfide bonding Animals Humans Immunology and Allergy Amino Acid Sequence Cysteine Disulfides Immunoglobulin Allotypes Peptide sequence Cysteine metabolism Chemistry Mutagenesis Immunoglobulin A Immunoglobulin Isotypes Biochemistry Covalent bond Mutagenesis Site-Directed Immunoglobulin Light Chains Protein folding Protein Processing Post-Translational |
| Zdroj: | The Journal of Immunology. 169:5072-5077 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.9.5072 |
| Popis: | In humans, there are two subclasses of IgA, IgA1 and IgA2, with IgA2 existing as three allotypes, IgA2m(1), IgA2m(2) and IgA2(n). In IgA1, Cys133 in CH1 forms the disulfide bond to the L chain. Our previous studies indicated that in IgA2 lacking Cys133, a disulfide bond forms between the α-chain and the L chain when Cys220 is followed by Arg221, but not when Cys220 is followed by Pro221, suggesting that the Cys in CH1 might be involved in disulfide bonding to the L chain. However, here we show that covalent assembly of the H and L chains in IgA2(n) requires hinge-proximal Cys241 and Cys242 in CH2 and not Cys196 or Cys220 in CH1. Using pulse-chase experiments, we have demonstrated that wild-type IgA2(n) with Arg221 and Cys241 and Cys242 assembles through a disulfide-bonded HL intermediate. In contrast, the major intermediate for IgA2 m(1) with Pro221 assembly was H2 even though both Cys241 and Cys242 were present. Only a small fraction of IgA2 m(1) assembles through disulfide-bonded HL. Overall, our studies indicate that for IgA2 covalent assembly of the H and L chains requires the hinge-proximal cysteines in CH2 and that the structure of CH1 influences the efficiency with which this covalent bond forms. |
| Databáze: | OpenAIRE |
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