RTX toxin structure and function: a story of numerous anomalies and few analogies in toxin biology.
It can be agreed that RTX toxins contribute to the pathogenesis of different diseases by causing dysfunction of the general cellular reactions of the immune response. The suggestion that RTX toxins induce cytokine production in nonimmune cells that would ultimately cause tissue damage is an expansion of their role in disease pathogenesis (Uhlen et al. 2000). Investigators in the RTX toxin field may not agree with me, but precise and satisfactory answers to the following questions are not yet available. How do RTX toxins mechanistically damage a cell? Do RTX toxins have receptors in the classic sense, in which there is a reversible ligand and receptor complex? What is responsible for the common Ca2+ ion influx in affected cells? The recent observation that an RTX toxin stimulates host-cell-mediated Ca2+ ion oscillation in part challenges the long held concept that these toxins damage cells by the direct formation of pores. Are the Ca2+ ion fluxes truly the noxious cellular insult? What is the final molecular structure of RTX toxins at the time they cause cellular death? How does the common requirement for acyl modification among RTX toxins fit into the toxin structure and mechanism of cellular killing, particularly when mixtures of unusual fatty acids are used by some toxins? There are a number of outstanding laboratories throughout the world that are seeking answers to these questions. We can reasonably expect that during the next decade research on the structure and function of RTX toxins will lead to new chemotherapeutic targets and reagents for basic cell biology and biotechnology.
Welch
R A
RA
Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine, Madison, WI 53706, USA.
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability; D003603:Cytotoxins / Q000737:chemistry* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000378:metabolism* / Q000472:pathogenicity; D006460:Hemolysin Proteins; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D006460:Hemolysin Proteins; D008070:Lipopolysaccharides; C087744:ApxI toxin, Bacteria