Antibody constant region: potential to bind metal and nucleic acid.
Environmental challenges appear to elicit similar patterns of cellular responses such as positive autoregulation and autoamplification whether one considers the generation of antibodies with identical antigen specificity or the accumulation of host-protective transcription factors. Therefore, I analyzed the structure of immunoglobulins (Ig) for motifs commonly found in transcription factors. Specifically, the well-known abundance and periodic location of cysteine residues in immunoglobulin chains prompted me to check antibody constant regions for the presence of putative metal-binding domains and zinc finger-like sequences. The constant regions of Ig light and heavy chains were found to harbor one or several copies, respectively, of a short cysteine- and histidine-containing sequence. Moreover, all four IgG subclasses were detected to comprise zinc finger-like motifs in their heavy chain constant and hinge domains. Yet another finding is the occurrence of several sequences of the form serine-proline-X-X and/or threonine-proline-X-X in the hinge sections of IgA and IgG3. These results suggest that antibody constant regions, as a fragment and/or embedded in a full-length immunoglobulin chain, may complex metal, thus acquiring conformations conducive to dimerization and nucleic acid binding. As such, my study provides a putative structural basis for the known requirement of divalent metal cations, particularly of zinc ions, for a normal immune response, and warrants further investigations, both theoretical and experimental, into the potential of antibody constant regions for metal binding and gene regulation. Moreover, future testing of the proposed zinc finger peptides from Ig constant domains should yield information relevant to zinc finger design with potentially wide applications in research and clinical medicine.(ABSTRACT TRUNCATED AT 250 WORDS)
Radulescu
R T
RT
Molecular Concepts Research (MCR), Munich, Germany.
D000595:Amino Acid Sequence; D005075:Biological Evolution; D003545:Cysteine; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D008957:Models, Genetic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D008670:Metals; D012367:RNA, Viral; D014157:Transcription Factors; D015032:Zinc; D003545:Cysteine