Amino acid sequence homology between ligands and their receptors: potential identification of binding sites.
Mice were immunized with alpha-bungarotoxin (BGT), a nearly irreversible antagonist of the acetylcholine receptor (AChR), to produce monoclonal antibodies (Mabs). One of the Mabs (JMC2.7) bound not only to BGT, but to the AChR as well. To understand the molecular basis for this novel cross-reaction, the amino acid sequences of these proteins were searched for areas of similarity which might constitute the shared epitope. A number of short segments of sequence homology were found, one of them representing the BGT-binding site of the AChR. Because a portion of BGT resembles that part of the AChR that binds toxin, the self-binding of BGT was evaluated. As shown here, BGT binds specifically to itself to form dimers. In order to extend these observations, other ligand-receptor pairs were examined for sequence homology. The sodium channel and alpha-scorpion toxins were found to have distinct areas of similarity, as do interleukin 2 (IL-2) and the IL-2 receptor. As a general principle, we propose that peptide ligands and their receptors may often share amino acid sequence homology. In fact, the sites of interaction between two proteins may largely be determined by these regions of similarity.
Department of Psychiatry, University of Alabama, Birmingham 35294.
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Dwyer
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D004557:Electric Organ / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014101:Torpedo
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D008024:Ligands; D011950:Receptors, Cholinergic