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K Adetugbo

Publications and source records attributed to K Adetugbo.

10 recordsLinked to original sources
PubMed1978

Evolution of immunoglobulin subclasses. Primary structure of a murine myeloma gamma1 chain.

The amino acid sequences of the first six CNBr fragments (303 residues) of MOPC 21 heavy chain have been determined, using conventional techniques. This completes the determination of the covalent structure of MOPC 21 immunoglobulin (IgG1, K). MOPC 21 gamma1 chain is a unique sequence of 440 amino acid residues. The variable region is homologous with human VHIII sequences. A comparison of the constant region with homologous sequences shows that mouse gamma1 and gamma2 proteins differ much more than the gamma subclasses in man and in some other species and supports earlier suggestions that mouse gamma1 and the four human gamma subclasses have a common ancestor different from the mouse gamma2 ancestor. Unlike some other subclasses, but like those in the guinea pig, mouse gamma1 and gamma2 genes have diverged before speciation. An expansion-contraction mechanism is proposed for the evolution of gamma genes.

Amino Acid Sequence↗
PubMed1978

Spontaneous somatic mutations. Structural studies on mutant immunoglobulins.

The precise alterations in the protein amino acid sequences of the immunoglobulin heavy chains of spontaneously arisen MOPC 21 mutant clones IF2 and IF1 have been determined. All the cyanogen bromide fra-ments of both heavy chains have been isolated and compared to the wild type CNBr fragments. For IF2, there is an internal deletion, from the wild type sequence, of 96 amino acids, from residues 121 to 215 inclusive. Moreover, in IF2, there are no disulfide bonds formed between heavy and light chains, presumably because of the deletion of the CH1 pseudosubunit. There are no other alterations in its covalent structure. For IF1, there is a deletion of the COOH-terminal 83 amino acids (residues 358 to 440, inclusive). Although IF1 heavy chain behaves on dodecyl sulfate-polyacryl-amide gels as if it were only 10 to 15 residues shorter than wild type, no other amino acid sequence differences from wild type are found. IF1 arose most likely by a nonsense mutation of a serine codon. For IF2, whose deletion is like that seen in some human heavy chain disease proteins, the most likely explanation is an error of recombination. The structure of IF2 suggests that the heavy chain variable region ends at a position homologous to residue 120 of the MOPC 21 heavy chain.

Amino Acids↗
PubMed1978

Expression of antibody genes in tissue culture: structural mutants and hybrid cells.

Detailed information on the nature and frequency of somatic mutations has been derived from studies of the clonal diversification of the myeloma MOPC 21 in tissue culture. A screening procedure is described that permitted the isolation of four spontaneous mutations at the gamma1 structural gene locus. These originate from four mutation events. Two seem to be point mutations: a "nonsense" and a "mis-sense." Of the other two, one is a frameshift leading to mistranslation and early termination, the other a large deletion due to perhaps an intrachromosomal translocation or a mitotic recombination. Fusion between myeloma-producing cells has shown that variable and constant region genes cannot be scrambled. Differentiation from stem to plasma cells seems to involve changes in the primary sequence of the DNA. Fusion between myeloma cells and spleen cells from immunized animals is a satisfactory method for the derivation of permanent tissue culture lines producing specific antibody. The hybrids express the myeloma as well as the specific antibody light and heavy chains. By subcloning and selection, one can derive lines that selectively lose individual chains. Lines that no longer express the myeloma components can thus be derived. The use of appropriate defective variants of the myeloma parental line is another way of avoiding the presence of the myeloma components.

Animals↗
PubMed1977

Molecular analysis of spontaneous somatic mutants.

Eukaryotic structural gene mutations occurring spontaneously in a mouse myeloma cell line offer the opportunity to study somatic mutation in animal cells at the molecular level. Studies on the myeloma protein and on mRNA have enabled us to characterise four such mutants representing four different mutation mechanisms. The results may have some bearing on the origin of antibody diversity.

Amino Acid Sequence↗
PubMed1975

Mouse immunoglobulin subclasses: cyanogen bromide fragments and partial sequence of a gamma1 chain.

The purification and characterisation of all the cyanogen bromide fragments of MOPC 21 heavy (gamma1) chain is described. The ten BrCN fragments account for the whole chain. Four of these fragments have been used to establish the sequence of the C-terminal stretch (138 residues) that includes the entire CH3 and a part of the CH2 homology regions. A comparison of this sequence with homologous sequences is presented. Mouse gamma1 and gamma2 proteins differ much more than the gamma subclasses in humans and in other species. The comparison further suggests that the four human gamma subclasses and mouse gamma1 have a common ancestor which differs from the mouse gamma2 ancestor. Unlike other subclasses, mouse gamma1 and gamma2 genes have diverged before speciation.

Amino Acid Sequence↗