Vol. 160, No. 1, 1969 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS April 14, 1969 Pages 333-339 DOMAIN-SPECIFIC BIAS IN ARGININE/LYSINE USAGE BY PROTEIN TOXINS Erwin London and Cindy L. Luongo Department of Biochemistry, State University of New York, Stony Brook, New York 11794-5215 Received February 1, 1989 The content of lysine and arginine residues in a number of A-B type protein toxins has been examined. It is found that the A subunit, or its equivalent, often shows a strong bias in the type of basic amino acid residue used tending towards nearly exclusive use of either arginine or lysine rather than use of both, whereas the B subunit or its equivalent shows no such bias. Although arginine codons are GC-rich and lysine codons are AT-rich, the content of GC and AT in the genes coding for the toxins does not adequately explain this bias. Other explanations are discussed, including the possibility that the bias is linked to catalytic function or membrane interaction. Understanding this bias may yield valuable insights into toxin structure and function. Furthermore, identification of bias in sequences may be a useful tool for identifying new toxins and their domains. 0 1989 Academic Press, Inc. Protein toxins of various types have been identified. One such type of toxin is the A-B class of toxins of medium molecular weight. These toxins have become targets of intensive research for a variety of reasons including the insights they give into membrane signalling and translocation processes, the interest in development of immunoglobulin-toxin hybrids (immunotoxins) as therapeutic agents, and the similarities between toxin and viral entry into cells. In these proteins the toxic enzymatic activity is generally carried by the A subunit, while the B subunit both carries the cell receptor binding activity and aids the penetration of the A subunit into the cytoplasm. The A-B toxins have a variety of enzymatic activities including the following: ADP-ribosylation of the modified His residue (diphthamide) of elongation factor 2 (1) in the case of diphtheria toxin (DT) and Pseudomonas exotoxin A (PE); ADP-ribosylation of the adenylate cyclase regulating G-proteins in the case of cholera toxin, the closely related E. coli heat-labile toxin, and -- pertussis toxin (2,3), and removal of the adenine base at position 4324 in 28s rRNA in the case of ricin, Shiga toxin, and presumably Shiga-like toxin of E. coli (4,5). Although different classes of A-B toxins appear to share only very little amino acid homology (6,7) and apparently catalyze quite different processes, all the toxins listed above cleave ribose l-carbon to nitrogen bonds, and therefore their activities are related. Recently, we 0006-291X/89 $1.50 333 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.