Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins
Autor: | Joel Moss, B. C. Kunz, E. M. Twiddy, Ronald Adamik, S. R. Price, R. K. Holmes, Chii-Ming Lee, Su-Chen Tsai, Patrick P. Chang |
---|---|
Rok vydání: | 1991 |
Předmět: |
Cholera Toxin
ADP ribosylation factor GTP' Bacterial Toxins Biology medicine.disease_cause Adenylyl cyclase chemistry.chemical_compound Enterotoxins GTP-binding protein regulators GTP-Binding Proteins medicine Escherichia coli Adenosine Diphosphate Ribose Adenosine diphosphate ribose ADP-Ribosylation Factors Escherichia coli Proteins Cholera toxin Membrane Proteins General Medicine Molecular biology Recombinant Proteins chemistry Biochemistry ADP-ribosylation Guanosine Triphosphate Agmatine Research Article |
Zdroj: | Scopus-Elsevier |
ISSN: | 0021-9738 |
Popis: | Escherichia coli heat-labile enterotoxins (LT) are responsible in part for "traveler's diarrhea" and related diarrheal illnesses. The family of LTs comprises two serogroups termed LT-I and LT-II; each serogroup includes two or more antigenic variants. The effects of LTs result from ADP ribosylation of Gs alpha, a stimulatory component of adenylyl cyclase; the mechanism of action is identical to that of cholera toxin (CT). The ADP-ribosyltransferase activity of CT is enhanced by 20-kD guanine nucleotide-binding proteins, known as ADP-ribosylation factors or ARFs. These proteins directly activate the CTA1 catalytic unit and stimulate its ADP ribosylation of Gs alpha, other proteins, and simple guanidino compounds (e.g., agmatine). Because of the similarities between CT and LTs, we investigated the effects of purified bovine brain ARF and a recombinant form of bovine ARF synthesized in Escherichia coli on LT activity. ARF enhanced the LT-I-, LT-IIa-, and LT-IIb-catalyzed ADP ribosylation of agmatine, as well as the auto-ADP ribosylation of the toxin catalytic unit. Stimulation of ADP-ribosylagmatine formation by LTs and CT in the presence of ARF was GTP dependent and enhanced by sodium dodecyl sulfate. With agmatine as substrate, LT-IIa and LT-IIb exhibited less than 1% the activity of CT and LT-Ih. CT and LTs catalyzed ADP-ribosyl-Gs alpha formation in a reaction dependent on ARF, GTP, and dimyristoyl phosphatidylcholine/cholate. With Gs alpha as substrate, the ADP-ribosyltransferase activities of the toxins were similar, although CT and LT-Ih appeared to be slightly more active than LT-IIa and LT-IIb. Thus, LT-IIa and LT-IIb appear to differ somewhat from CT and LT-Ih in substrate specificity. Responsiveness to stimulation by ARF, GTP, and phospholipid/detergent as well as the specificity of ADP-ribosyltransferase activity are functions of LTs from serogroups LT-I and LT-II that are shared with CT. |
Databáze: | OpenAIRE |
Externí odkaz: |