Amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob

Abstract

The amino acid sequence of the heavy-chain variable region of the crystallizable human myeloma protein Dob was determined. This protein has a deletion in the hinge region. The complete sequence was established by analysis, in the automated sequenator, of the intact Fd'' piece and of 3 large overlapping fragments prepared from Fd'' by digestion with CNBr, by tryptic digestion of the citraconylated Fd'' and by cleavage with hydroxylamine. Portions of the sequence were confirmed by examination of the amino acid composition and the partial sequence of a variety of small peptides obtained by enzymatic degradation. The Dob H-chain variable region appeared to belong to the VHIII subgroup, but there are several unusual substitutions. Residue 45 in the Dob sequence is proline, although all other known H-chain sequences in man, mouse, rabbit and guinea pig have leucine at this position. Positions 10 (aspartic acid), 68 (alanine) and 82 (leucine) in the Dob sequence are also atypical. There is no deleted segment in the variable region of the Dob H-chain nor any abnormality in the variable-constant joining region. The hinge-region deletion appears to be the only gross structural anomaly in the Dob H-chain.