Antibody-Mediated Activation of Genetically Defective Escherichia Coli Galactosidases by Monoclonal Antibodies
The effects of antibody binding on protein conformation can be dramatic, and some examples have been known for several years. A great deal of information has been gathered recently from Escherichia coli β-galactosidase, a tetrameric enzyme of Mr 465,000 composed of four identical subunits. By using wild-type enzyme and a battery of mutant products first as immunogens and then as antigens in a series of serological reactions, a number of “conformational effects” have been discovered in this system1. These include (a) protection from thermal denaturation; (b) activation of defective enzyme; (c) facilitation of complementation between deletion products; and (d) inactivation of native enzyme. Apparently, with the exception of the first one, in which the antigen and the immunogen used to raise antibody are identical and the immune interaction stabilizes the conformation of the antigen molecule, all other cases involve a change in the tertiary or quaternary conformation of the enzyme. Such a mechanism may require antibodies directed toward conformation dependent determinants which are capable of interacting with these determinants even when the molecular conformation is modified, or unstable.
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