The Structure of Bence-Jones Proteins: the Work of Frank W. Putnam

Abstract

The Amino Acid Sequence of a κ Type Bence-Jones Protein. III. The Complete Sequence and the Location of the Disulfide Bridges (Titani, K., Shinoda, T., and Putnam, F. W. (1969) J. Biol. Chem. 244, 3550–3560) The Amino Acid Sequence of a λ Type Bence-Jones Protein. III. The Complete Amino Acid Sequence and the Location of the Disulfide Bridges (Titani, K, Wikler, M., Shinoda, T., and Putnam, F. W. (1970) J. Biol. Chem. 245, 2171–2176) Frank William Putnam (1917–2006) was born in New Britain, Connecticut. He attended Wesleyan University and received his B.A. in chemistry in 1939 and an M.A. in chemistry in 1940. In 1942 he received his Ph.D. in biochemistry from the University of Minnesota. Putnam began his career in biochemistry as an instructor at Duke University's School of Medicine, working with Hans Neurath, who was the subject of a previous Journal of Biological Chemistry (JBC) Classic (1JBC Classics: Schwert, G. W., Neurath, H., Kaufman, S., and Snoke, J. E. (1948) J. Biol. Chem. 172, 221–239; Davie, E. W., and Neurath, H. (1955) J. Biol. Chem. 212, 515–530 (http://www.jbc.org/cgi/content/full/280/2/e1)Google Scholar). In 1947 Putnam left Duke to become an Assistant Professor in Biochemistry at the University of Chicago and was promoted to Associate Professor in 1953. Two years later, he was named Head of Biochemistry at the University of Florida, a position he held until 1965. From Florida, he moved to Indiana University to become a Professor of Biology and the Director of the Division of Biological Sciences. He held this position until 1969 when he resigned to devote his time to teaching and research. In 1969 Putnam was named Professor of Molecular Biology and Zoology at Indiana. In 1971 he became Professor of Biochemistry at the Indiana University Medical School, and three years later he became Distinguished Professor of Molecular Biology and Biochemistry. In 1988 he became Distinguished Professor Emeritus at Indiana University. Putnam's early research focused on developing methods for determining the molecular structure of proteins. Later, he turned to the biology and chemistry of bacterial viruses, which led to his study of the Bence-Jones proteins, the subject of the two JBC Classic papers reprinted here. Bence-Jones proteins consist of monoclonal light chains of γ-globulin molecules. They occur in the urine of patients with multiple myeloma and are considered to be tumor markers. The light chains contain an amino-terminal variable region (residues 1–108) and a carboxyl-terminal constant region (residues 109–214). There are two types of Bence-Jones protein light chains: κ and λ. The first Classic deals with Putnam's elucidation of the amino acid sequence and location of the disulfide bridges in human κ Bence-Jones protein Ag. He determined the 214-amino acid sequence by analyzing the sequences of tryptic and chymotryptic peptides from the carboxymethylated protein, the aminoethylated protein, and the disulfide bridge peptides. Comparing this sequence to those of other known human κ Bence-Jones proteins, Putnam discovered that, “these proteins differ in many positions in the amino-terminal or variable half of the molecule but appear to have an identical sequence in the carboxy-terminal or constant half except for a substitution at position 191 that is correlated with the Inv genetic factor.” Using similar methods, Putnam then determined the sequence and location of the disulfide bridges in the human λ Bence-Jones protein Sh. He then compared this sequence to the sequences of other human λ Bence-Jones proteins and confirmed his earlier observations with the κ proteins. Namely, that the amino-terminal half of the protein has great variation in sequence while the carboxyl-terminal portion of the molecule has a constant sequence. He also noted that Sh is homologous to both the human and mouse κ chains, indicating a common ancestral gene. This work by Putnam on the κ- and λ-immunoglobulin light chains provided some of the first indications of the constant and variable regions in any immunoglobulin molecule. In recognition of his contributions to science, Putnam was elected to the National Academy of Sciences and the American Academy of Arts and Sciences and was an honorary fellow of the National Academy of Clinical Biochemistry. Putnam also served as Secretary of the American Society for Biochemistry and Molecular Biology from 1958 to 1963, was chairman of the Divisional Committee for Institutional Programs of the National Science Foundation, was a member of the National Advisory General Medical Sciences Council of the National Institutes of Health, and was elected chairman of the Division of Biological Chemistry of the American Chemical Society. He also received the Sword of Hope Award from the American Cancer Society for his work in basic cancer research.