2kc8 | pdb_00002kc8

Structure of E. coli toxin RelE (R81A/R83A) mutant in complex with antitoxin RelBc (K47-L79) peptide

spinqualitylabelsall models 2kc8, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2kc8 is a 2 chain structure with sequence from Ecoli. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 2kc9 Gene: relE, b1563, JW1555 (ECOLI), relB, b1564, JW1556 (ECOLI) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RELE_ECOLI] Toxic component of a toxin-antitoxin (TA) module. A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). Acts by cleaving mRNA with high codon specificity in the ribosomal A site between positions 2 and 3. The stop codon UAG is cleaved at a fast rate while UAA and UGA are cleaved with intermediate and slow rates. mRNA cleavage can also occur in the ribosomal E site after peptide release from peptidyl-tRNA in the P site as well as on free 30S subunits. Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is inhibited by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow or die in presence of bactericidal agent and are largely responsible for high levels of biofilm tolerance to antimicrobials). Acts with RelB as a corepressor of relBE transcription. Seems to be a principal mediator of cell death in liquid media. [RELB_ECOLI] Antitoxin component of a toxin-antitoxin (TA) module. Counteracts the effect of RelE via direct protein-protein interaction, enabling the reversion of translation inhibition. Also acts as an autorepressor of relBE transcription. DNA-binding and repression is stronger when complexed with corepressor RelE. Increased transcription rate of relBE and activation of relE is consistent with a lower level of RelB in starved cells due to degradation of RelB by protease Lon. Seems to be a principal mediator of cell death in liquid media. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In Escherichia coli, RelE toxin participates in growth arrest and cell death by inducing mRNA degradation at the ribosomal A-site under stress conditions. The NMR structures of a mutant of E. coli RelE toxin, RelE(R81A/R83A), with reduced toxicity and its complex with an inhibitory peptide from RelB antitoxin, RelB(C) (Lys(47)-Leu(79)), have been determined. In the free RelE(R81A/R83A) structure, helix alpha4 at the C terminus adopts a closed conformation contacting with the beta-sheet core and adjacent loops. In the RelE(R81A/R83A)-RelB(C) complex, helix alpha3(*) of RelB(C) displaces alpha4 of RelE(R81A/R83A) from the binding site on the beta-sheet core. This helix replacement results in neutralization of a conserved positively charged cluster of RelE by acidic residues from alpha3(*) of RelB. The released helix alpha4 becomes unfolded, adopting an open conformation with increased mobility. The displacement of alpha4 disrupts the geometry of critical residues, including Arg(81) and Tyr(87), in a putative active site of RelE toxin. Our structures indicate that RelB counteracts the toxic activity of RelE by displacing alpha4 helix from the catalytically competent position found in the free RelE structure. Inhibitory mechanism of Escherichia coli RelE-RelB toxin-antitoxin module involves a helix displacement near an mRNA interferase active site.,Li GY, Zhang Y, Inouye M, Ikura M J Biol Chem. 2009 May 22;284(21):14628-36. Epub 2009 Mar 18. PMID:19297318 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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