Immunoglobulins, biosynthesis

Williamson, A.R., Singer, H.H., Singer, P.A. Mosmann, T.R. (1980) The Value of Tunicamycin for Studies on Immunoglobulin Biosynthesis , Biochemical Society Transactions, 8, 168-70... 

The available evidence indicates that immunoglobulin biosynthesis takes place largely on polyribosomes bound to membrane surfaces in the rough endoplasmic reticulum of lymphoid cells (145-147) the polyribosomes are present in the microsomal fraction isolated from a cell homogenate. The possibility that some biosynthesis may occur on free polyribosomes has not been rigorously excluded. After release from the polyribosome an immunoglobulin molecule traverses the membrane into the cisternal compartment where it travels to the smooth endoplasmic reticulum (devoid of polyribosomes) and to the Golgi vesicles, prior to its release from the cell. 

The availability of purihed antibodies permitted the detailed characterization of the different classes of immunoglobulins with respect to their biosynthesis, metabolism, and composition in plasma (Table 10.2). The most abundant immunoglobulin molecule in serum is IgG. IgG classes 1,2,... 

Fig. 3.3 FVIII biosynthesis. Signal peptide cleavage and asparagine (N)-linked glycosylation of the FVIII occurs after translation and translocation to the lumen of the endoplasmic reticulum (ER). Within the ER, the FVIII is folded, which requires binding to chaperone proteins. FVIII binds immunoglobulin-binding protein (BiP) at the A1 domain, and is released in an ATP-dependent step. Next, FVIII binds calnexin (CNX) and calreticulin (CRT) (not shown) at the B domain. Properly folded FVIII proteins are transported to the Golgi by chaperone proteins, LMANl and MCFD2 (not shown) for further processing LMANl also binds to the FVIII B domain. Incorrectly folded FVIII...

Analogs of 11, synthesized as (a) potential regulators of the biosynthesis, secretion, and function of immunoglobulins, include the N-[l-ethyl N-(benzyloxycarbonyl)]- (25) and N,N-dimethyl-2-(p-toluenesul-fonamido)succinamide (26), 5-hydrantoinacetic acid (27), 2-thio-5-hydantoinacetic acid (28), and 2,5-dioxopiperazine-3-acetic acid (29) derivatives, which were then O-deacetylated with sodium methoxide and (b) potential metabolic inhibitors of cellular-membrane glycoconju-gates, include the 1-N-glycyl derivative. 

Williamson, A. R., and B. A. Askonas. 1967. Biosynthesis of immunoglobulins the separate classes of polyribosomes synthesizing heavy and light chains. J. Molec. Biol., 23 201-215. 

However, data on the biosynthesis of a number of glycoproteins clearly suggest that the Golgi apparatus serves as an assembly line along which sugar moieties are sequentially added to such proteins as thyroglobu-lin and immunoglobulin [261]. 

Malignant cell lines, maintained in culture, have been extensively used in studies of the biosynthesis of H and L chains and their assembly into complete immunoglobulin molecules. An important current area of... 

The rate of biosynthesis of immunoglobulins in chickens, per unit body weight, is comparable to that observed in man. The half-lives of chicken IgM and IgG are 1.7 and 4.1 days, respectively, values one-third and one-fifth of those of the corresponding human proteins (90,91). 

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