By Frank W. Putnam
The Plasma Proteins V3
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Additional info for The Plasma Proteins. Structure, Function, and Genetic Control
In m o s t immunoglobulins and particularly in IgG and IgD the hinge region is uniquely susceptible to limited proteolysis to yiel d the F ab and Fc fragments. A p o p u l ar idea is that this section of the immunoglobulin molecule is flexible and that combination of antigen wit h antibody results in a conformational change in the F ab region that is reflected in a kind of allosteric w a y in the Fc region b y w a y of a flexing of the hinge region. Figure 5 shows schematically that the hinge region differs markedly in h u m an ì, a, and y h e a vy c h a i n s.
Y e t , in multiple m y e l o m a or macroglobulinemia, a single o ne of t h e se is selected for massive synthesis to the virtual exclusion of all o t h e r s. B e n ce J o n es protein m ay b e secreted into the s e r um and e x c r e t ed into the urine in either the m o n o m e r ic or dimeric form. B e n ce J o n es protein is identical in structure to the light chain of the m y e l o m a globulin or macroglobulin p r o d u c ed by the patient and is r e p r e s e n t a t i ve of normal light chains of either the ê or the ë t y p e .
T h u s, the n u m b er of methionine residues in the C region is of practical interest bec a u se this d e t e r m i n es the n u m b er of fragments obtainable by C N B r cleavage. S e q u e n ce analysis of such large polypeptid e chains requires prodigious effort and a combination of standard t e c h n i q u es and special strategies that differ for each chain. , 1973a). This w o r k required tryptic cleavage at 60°C to p r o d u ce F ab ì and ( F c ^ )5 fragments, r e d u c t i o n - a l k y l a t i on of whole IgM to separate the h e a vy and light c h a i n s, separate e n z y m a t i c digestion of the h e a vy chain wit h trypsin, c h y m o t r y p s i n, and thermolysin followe d by purification and s e q u e n ce analysis of the p e p t i d e s , C N B r cleavage of the whole I g M, the F ab and (Fc^t)5 fragments, and the h e a vy chain, and various o t h er p r o c e d u r e s.
The Plasma Proteins. Structure, Function, and Genetic Control by Frank W. Putnam