Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes

Biochemistry
J K SuhJ D Robertus

Abstract

Several pathogenic bacteria, including Shigelladysenteriae and certain strains of Escherichia coli, produce potent class 2 ribosome inhibiting proteins (RIPs) termed Shiga toxins (Stx). The toxins are bipartite molecules composed of a single A chain (StxA) noncovalently associated with a pentamer of receptor-binding B subunits (StxB). StxA and Stx1A from E. coli are protoxins. Proteolysis generates an A1 enzyme (28 kDa) and an A2 fragment (3 kDa), which remain bound, inactivating the enzyme, until a disulfide bond linking them is reduced. Efforts to express active recombinant Stx1A1 in the cytoplasm of E. coli were very difficult and led to the hypothesis that Stx1A1 is toxic to E. coli. We created the gene for a His-tagged Stx1A1 (cStx1A1) and expressed it in E. coli from a tightly controlled expression vector. About 1-2 mg of protein can be purified in a one-step isolation from 1 L of culture. cStx1A1, RTA, and PAP exhibited similar high toxicity against the Artemia ribosomes with IC50 values near 1 nM. Surprisingly, Stx1A1 had an IC50 of 0.8 nM against E. coli ribosomes, about the same as it had for Artemia ribosomes. This is about 250 times more active than PAP against bacterial targets, making Stx1A1 the most powerful RIP ...Continue Reading

References

May 6, 1975·European Journal of Biochemistry·G A KramerB A Hardesty
Oct 20, 1992·Journal of Molecular Biology·A F Monzingo, J D Robertus
Sep 5, 1991·Journal of Molecular Biology·Y EndoI G Wool
Jan 1, 1990·Methods in Enzymology·L Gold, G D Stormo
Mar 1, 1988·Journal of Bacteriology·N A StrockbineA D O'Brien
Jun 1, 1987·Microbiological Reviews·A D O'Brien, R K Holmes
Jun 1, 1994·Protein Expression and Purification·T M ZollmanC J Hovde
Jul 22, 1994·Science·R F Service
Oct 20, 1993·Journal of Molecular Biology·A F MonzingoJ D Robertus

❮ Previous
Next ❯

Citations

May 30, 2001·Microbes and Infection·E V O'Loughlin, R M Robins-Browne
Dec 7, 2002·The International Journal of Biochemistry & Cell Biology·F Javier AriasTomás Girbés
Dec 22, 2009·Nature Reviews. Microbiology·Ludger Johannes, Winfried Römer
Nov 10, 2011·Toxins·Elisabete ValérioRogério Tenreiro
Jan 17, 2012·Toxicon : Official Journal of the International Society on Toxinology·Walter J LapadulaMaximiliano Juri Ayub
May 25, 2010·Toxicon : Official Journal of the International Society on Toxinology·Yan BaiJon D Robertus
Mar 5, 2013·Toxicon : Official Journal of the International Society on Toxinology·Kerrie L MayNilgun E Tumer
Sep 3, 2016·Computer Methods and Programs in Biomedicine·Marwa Mostafa MostafaAmr Badr
Nov 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wei-Wei ShiPang-Chui Shaw
Apr 30, 1999·Emerging Infectious Diseases·C K SchmittA D O'Brien
May 23, 2002·FEBS Letters·T-A M YamamotoA Tunnacliffe
Dec 29, 2018·Protein and Peptide Letters·Vinita ChauhanRam Kumar Dhaked
Apr 4, 2019·Protein and Peptide Letters·UNKNOWN Fiorella Di Nicuolo, Monia Specchia, Lorenza Trentavizi, Alfredo Pontecorvi, Giovanni Scambiac and Nicoletta Di Simone
May 3, 2002·Clinical and Diagnostic Laboratory Immunology·P H M LeungW C Yam
Nov 26, 2003·Critical Reviews in Microbiology·Jason J LeBlanc
Sep 4, 2020·The Journal of Biological Chemistry·Michael J RudolphXiao-Ping Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.