Archaeal toxin-antitoxin RelB-RelE complex
Pyrococcus horikoshii (archaea, thermophile)
Many bacteria stop growth when nutrients are limited. Some of them may die, others, however, will survive by lowering energy consumption. Toxin-antitoxin pair is found to be an element of this mechanism. These genes are organized in an operon that encodes a toxin and an antitoxin. In steady state, antitoxins neutralize the effect of toxins by direct protein-protein interaction. In addition, antitoxins and toxin-antitoxin complexes bind to their promoter of their own operon and negatively regulate their own transcription. Upon environmental stresses, such as nutrient depletion, antitoxins are degraded to release the toxins; this results in the growth arrest. In the Escherichia coli chromosome, at least five toxin-antitoxin loci exist. An example is relBE; the gene products, RelE and RelB are a toxin and an antitoxin, respectively. In addition to the repression of their own gene transcription, RelE is reported to cleave mRNAs on the A site of ribosomes. relBE operon is also conserved in archaea. By the structural gemonics study, Takagi et al. identified that, in a hyperthermophilic archaeon, Pyrococcus horikoshii, the genes PHS103 and PHS104 have similar sequences to E. coli relB and relE genes, respectively. Hence, their gene products are named as aRelB and aRelE, respectively.
The structure described here is an aRelB-aRelE complex. An aRelB chain wrapping around the central beta-sheet of an aRelE is a unit of the complex. In the physiological condition, the complex seems to be composed of two units facing each other like other transcription factors. The interactions between them are hydrogen bonds and salt bridges. The hydrogen bonds are formed between the N- and C-terminal helices of aRelB and the central beta-sheet of aRelE. The salt bridges are formed between E31, D33, D35 and E40 of aRelB and K47, R58, R65 and K81 of aRelE, but these are not conserved among various species. Hence, the hydrogen bonds are considered to be the main interaction between aRelB and aRelE. Mutation analysis revealed that R85, in the C-terminal region, is strongly involved in the RNase activity of aRelE, whereas R40, L48, R58 and R65 play a modest role in the activity. These residues form cationic surface of aRelE and the electrostatic interactions between aRelB and aRelE conceal it. Therefore, this cationic surface is considered to be an RNase active site of the toxin, and the activity is inhibited by the interaction with antitoxin.
Protein Data Bank (PDB)
Takagi, H. Kakuta, Y. Okada, T. Yao, M. Tanaka, I. Kimura, M.; "Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects"; Nat.Struct.Mol.Biol.; (2005) 12:327-331 PubMed:15768033.
author: Daisuke Ino