Proton nuclear magnetic resonance studies of human immunoglobulins. Solution conformation of the constant domain of the .lambda. light chains and identification of the isotypes

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Abstract
Sixteen .lambda.-type Bence-Jones proteins [collected from the urine of patients with multiple myeloma] and 8 constant domain fragments of .lambda. chains were used to measure NMR signals of the C2.sbd. and C4.sbd.H protons of 2 histidine residues (His-189 and His-198) which exist in the constant half of the .lambda. chains. The pH titration curves for the C2.sbd.H proton signals of His-189 and His-198 of 6 Bence-Jones dimers were compared with those for the corresponding constant fragments. The tertiary structure of the constant domain apparently is well preserved even in the constant fragments which are known to exist as the monomer in solution. The C2.sbd. and C4.sbd.H proton peaks of His-198 can be used to identify the Mcg isotype. The chemical shifts of the C4.sbd.H proton of His-189 and His-198 can be used to detect the amino acid substitutions at positions 153 and 190 which are the Kern and Oz markers, respectively. Based on the NMR measurements, the Kern and at least 1 of the Mcg markers may be in close spatial proximity to His-189 and His-198, respectively. The NMR data were compared with the X-ray structure of the Fab fragment of human myeloma immunoglobulin, IgG1 (.lambda.) New. The NMR data are explained in terms of the crystal structure and are consistent with solution and crystal structure being quite similar in the constant domain of the .lambda. chain.