The Crystal Structure of the Intact E. coli RelBE Toxin-Antitoxin Complex Provides the Structural Basis for Conditional Cooperativity

TY - JOUR

T1 - The Crystal Structure of the Intact E. coli RelBE Toxin-Antitoxin Complex Provides the Structural Basis for Conditional Cooperativity

AU - Bøggild, Andreas

AU - Sofos, Nicholas

AU - Andersen, Kasper Røjkjær

AU - Feddersen, Ane

AU - Easter, Ashley D

AU - Passmore, Lori A

AU - Brodersen, Ditlev

N1 - Lab ID: 224 197

PY - 2012/10/10

Y1 - 2012/10/10

N2 - The bacterial relBE locus encodes a toxin-antitoxin complex in which the toxin, RelE, is capable of cleaving mRNA in the ribosomal A site cotranslationally. The antitoxin, RelB, both binds and inhibits RelE, and regulates transcription through operator binding and conditional cooperativity controlled by RelE. Here, we present the crystal structure of the intact Escherichia coli RelB(2)E(2) complex at 2.8 Å resolution, comprising both the RelB-inhibited RelE and the RelB dimerization domain that binds DNA. RelE and RelB associate into a V-shaped heterotetrameric complex with the ribbon-helix-helix (RHH) dimerization domain at the apex. Our structure supports a model in which relO is optimally bound by two adjacent RelB(2)E heterotrimeric units, and is not compatible with concomitant binding of two RelB(2)E(2) heterotetramers. The results thus provide a firm basis for understanding the model of conditional cooperativity at the molecular level.

AB - The bacterial relBE locus encodes a toxin-antitoxin complex in which the toxin, RelE, is capable of cleaving mRNA in the ribosomal A site cotranslationally. The antitoxin, RelB, both binds and inhibits RelE, and regulates transcription through operator binding and conditional cooperativity controlled by RelE. Here, we present the crystal structure of the intact Escherichia coli RelB(2)E(2) complex at 2.8 Å resolution, comprising both the RelB-inhibited RelE and the RelB dimerization domain that binds DNA. RelE and RelB associate into a V-shaped heterotetrameric complex with the ribbon-helix-helix (RHH) dimerization domain at the apex. Our structure supports a model in which relO is optimally bound by two adjacent RelB(2)E heterotrimeric units, and is not compatible with concomitant binding of two RelB(2)E(2) heterotetramers. The results thus provide a firm basis for understanding the model of conditional cooperativity at the molecular level.

U2 - 10.1016/j.str.2012.08.017

DO - 10.1016/j.str.2012.08.017

M3 - Journal article

C2 - 22981948

SN - 0969-2126

VL - 20

SP - 1641

EP - 1648

JO - Structure

JF - Structure

IS - 10

ER -