Human immunoglobulin subclasses. Partial amino acid sequence of the constant region of a γ4 chain

Pink, J. R. L.; Buttery, S. H.; Vries, Glen M. de; Milstein, C.

doi:10.1042/bj1170033

Cited by 91 publications

(42 citation statements)

References 37 publications

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“…The Cy regions of human IgG molecules are divided into four subclasses (Cy,, Cy2, Cy3, and C,4) encoded by distinct germ-line genes (1). Protein sequence studies (2)(3)(4)(5) have shown that the subclasses are highly homologous, indicating that the corresponding genes derive from a common ancestral Cy gene.…”

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confidence: 99%

Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.

Ellison¹,

Hood²

1982

Proc. Natl. Acad. Sci. U.S.A.

109

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We report the nucleotide sequence of a gene encoding a human immunoglobulin Cy,2 region. Comparison with the previously determined C,,4 sequence reveals that these two genes share extensive (=95%) homology in the three CH domain exons and adjacent noncoding regions. In contrast, hinge exons have diverged to a much greater degree, implying that natural selection has favored the generation ofdiversity in these coding regions. We have used the .noncoding nucleotide differences to estimate that approximately 6-7 millionyears have elapsed since the occurrence of the gene duplication or correction event which generated the two identical ancestral genes. In addition we show that the two C,, genes are arranged in human chromosomal DNA in the configuration 5'-C,2-17 kilobase pairs -C,,4-3'.

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confidence: 99%

Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.

Ellison¹,

Hood²

1982

Proc. Natl. Acad. Sci. U.S.A.

109

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“…reported for y4 heavy chain (22,24). The presence of Leu instead of Pro at the penultimate position is characteristic of the y4 subclass.…”

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confidence: 93%

“…The partial aminoacid sequence of the purified carboxymethylcysteine peptides is shown in Table 1. By comparison with proteins Eu (5) and Vin (22), the sequences found in the Hal peptides suggest that the peptides originate in the Fc fragment. Diagonal map electrophoresis showed them to be bridged as indicated in Table 1.…”

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confidence: 99%

“…Cysteines 261 and 321 (Table 1) were present in peak I and cysteines 367 and 425 in peak II. Peak III contained no homoserine and its NH2 terminal was His. Trypsin digestion released a peptide whose sequence corresponds to that of the C-terminal sequences previously (6,22). t A related (more basic) peptide was also obtained in low yield; its sequence is Lys-Cys-Lys (see also Fig.…”

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confidence: 99%

“…The first 10 residues in protein Hal come from the variable region (Hv). The first Met corresponds to position 252; from there on the sequence is identical to Vin, a y4 chain (22). the partial aminoacid sequence and alignment of CNBr fragments.…”

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confidence: 99%

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Protein Hal: Partial Deletion of a “γ” Immunoglobulin Gene(s) and Apparent Reinitiation at an Internal AUG Codon

Frangione

Lee

Haber

et al. 1973

Proc. Natl. Acad. Sci. U.S.A.

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Protein Hal is a human y4 heavy-chain disease protein whose molecular weight is reduced from 55,000 to 25,000 in 6 M guanidine due to the lack of disulfide bonds between heavy chains. Studies of aminoacid sequence indicate that it contains a gap of about 240 residues, starting 10 residues from the N-terminal end and including the rest of the Fd fragment, as well as the hinge region. Normal sequence apparently resumes at a methionine residue (position 252) in the second constant domain (CH2) and seems normal from there to the carboxyl end of the molecule. These results imply that reinitiation of translation at an internal AUG codon occurs in protein Hal.Gamma heavy-chain disease ('yHCD) is characterized by the presence in serum and urine of a protein related structurally to the Fc fragment of immunoglobulin heavy chains of humans (1). Interest in these natural fragments was stimulated when it was shown that the THCD proteins were not extracellular degradation products, but rather the result of abnormalities of gene expression. Thus, if more than one gene was involved in the synthesis of a single heavy chain, then the HCD proteins could result from a mutation affecting only one of them.Detailed structural studies (2-4) on three 'yHCD proteins have shown the defect to be an internal deletion of part of the Fd fragment, with resumption of normal sequence at the glutamic acid residues present at position 216 (the numbering sequence is appropriate for the yl heavy chain). This point marks the beginning of the hinge region, a section of the heavy chain between CH1 and CH2 domains (5), which contains the interheavy-chain disulfide bonds and is unique in not having a homologous counterpart in the remainder of the molecule (6, 7). These data suggested the possibility that the constant (C) region of immunoglobulin heavy chain was under the control of more than one gene and that position 216 could mark the beginning of another cistron (3). Although other interpretations are also possible (8-10), the finding of protein Meg (11), a myeloma protein with a deletion of a portion of the hinge region only, further emphasized the importance of position 216. The sequence of Mcg heavy chain shows that it is normal through the first 215 residues and has a gap of 15 amino acids that commences at position 216.Abbreviations: Nomenclature of immunoglobulins and their chains and fragments follows the recommendation of World Health Organization [Bull. WHO 30, 447 (1964); 33, 721 (1965); 35, 953 (1966); 38, 151 (1968) MATERIALS AND METHODSIsolation of the Hal Protein. The source of the Hal protein was a patient with malignant lymphoma accompanied by the presence in serum, urine, and pleural and peritoneal fluids of a gamma heavy-chain fragment belonging to the IgG4 subclass (12). All studies were performed on pleural or peritoneal fluid collected on ice and cleared of cellular debris by centrifugation before storage at -20°.Pleural fluid was adjusted to 20% saturation with ammonium sulfate. The resulting precipitate was removed by ...

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Characterization of disulfide linkages at the hinge region of IgG antibodies by HPLC mass spectrometry

You

Shi

Zhu³

et al. 2018

Biomedical Chromatography

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There are two types of disulfide linkages in IgG antibodies at the hinge region: intra- and inter-disulfide linkages. Characterization of intra-disulfide linked isomer will provide important information on the stability of the antibodies and better understanding of the mechanism of Fab-arm exchange. In this report, HPLC coupled with high-resolution mass spectrometry was applied for characterization of disulfide linkages in IgG antibodies at the hinge region. We were able to accurately identify both inter- and intra-disulfide linked peptides and correctly quantify intra-disulfide isomers. It is the first study to quantify intra-disulfide isomers in IgG antibodies with a mass spectrometry approach. It will help to achieve efficient generation of bispecific antibodies with Fab-arm exchange.

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Human immunoglobulin subclasses. Partial amino acid sequence of the constant region of a γ4 chain

Cited by 91 publications

References 37 publications

Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.

Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.

Protein Hal: Partial Deletion of a “γ” Immunoglobulin Gene(s) and Apparent Reinitiation at an Internal AUG Codon

Characterization of disulfide linkages at the hinge region of IgG antibodies by HPLC mass spectrometry

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