The yefM-yoeB toxin-antitoxin systems of Escherichia coli and Streptococcus pneumoniae: functional and structural correlation.
Toxin-antitoxin loci belonging to the yefM-yoeB family are located in the chromosome or in some plasmids of several bacteria. We cloned the yefM-yoeB locus of Streptococcus pneumoniae, and these genes encode bona fide antitoxin (YefM(Spn)) and toxin (YoeB(Spn)) products. We showed that overproduction of YoeB(Spn) is toxic to Escherichia coli cells, leading to severe inhibition of cell growth and to a reduction in cell viability; this toxicity was more pronounced in an E. coli B strain than in two E. coli K-12 strains. The YoeB(Spn)-mediated toxicity could be reversed by the cognate antitoxin, YefM(Spn), but not by overproduction of the E. coli YefM antitoxin. The pneumococcal proteins were purified and were shown to interact with each other both in vitro and in vivo. Far-UV circular dichroism analyses indicated that the pneumococcal antitoxin was partially, but not totally, unfolded and was different than its E. coli counterpart. Molecular modeling showed that the toxins belonging to the family were homologous, whereas the antitoxins appeared to be specifically designed for each bacterial locus; thus, the toxin-antitoxin interactions were adapted to the different bacterial environmental conditions. Both structural features, folding and the molecular modeled structure, could explain the lack of cross-complementation between the pneumococcal and E. coli antitoxins.
Nieto
Concha
C
Department of Protein Structure and Function, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu, 9, E-28040 Madrid, Spain.
Cherny
Izhack
I
Khoo
Seok Kooi
SK
de Lacoba
Mario García
MG
Chan
Wai Ting
WT
Yeo
Chew Chieng
CC
Gazit
Ehud
E
Espinosa
Manuel
M
D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002470:Cell Survival / Q000502:physiology; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D005810:Multigene Family; D049070:Protease La / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D013997:Time Factors
D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; C484519:YefM protein, E coli; C504245:YoeB protein, E coli; C483567:Lon protein, E coli; D049070:Protease La