An active derivative of rabbit antibody light chain composed of the constant and the variable domains held together only by a native disulfide bond.

Abstract:

:The immunoglobulin light chain is thought to be organized into two structural domains, the constant and the variable regions, linked by a switch region of lesser tertiary organization. Light chains of homogeneous rabbit antibodies to pneumococcal polysaccharides labeled with (125)I were subjected to trypsin digestion at different temperatures. At 43 degrees molecular size (as determined by gel filtration) remained unchanged until the chain was subjected to full reduction and alkylation, when half molecules were demonstrated. One light chain resisted tryptic digestion at 43 degrees . At 50 degrees extensive digestion to small peptides occurred. These experiments confirm the susceptibility of the switch region to enzymatic attack as well as the relative resistance of the constant and variable region domains. They also demonstrate that the third disulfide bridge in rabbit light chain extends between the two structural domains and maintains the integrity of the molecule even when a peptide bond in the switch region is cleaved. When the light chain was subjected to dilute acid hydrolysis [10% acetic acid-pyridine (pH 2.5) in 7 M guanidine-HCl for 24-90 hr] selective cleavage at the switch region was demonstrated in yields up to 90%. The site of cleavage was shown to be the acid labile Asp 109-Pro 110 bond by automated Edman degradation. After cleavage the molecule remained intact until full reduction and alkylation, when half molecules were again demonstrated. A light chain cleaved in this way with its interdomain disulfide bond intact, was able to recombine with a homologous heavy chain and restore antigen binding. This indicates that an intact switch region is not needed for antibody activity. The availability of a functional variable region now allows for planning an examination of the antibody combining site by the technique of peptide synthesis.

authors

Poulsen K,Fraser KJ,Haber E

doi

10.1073/pnas.69.9.2495

subject

Has Abstract

pub_date

1972-09-01 00:00:00

pages

2495-9

issue

9

eissn

0027-8424

issn

1091-6490

journal_volume

69

pub_type

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