The E. coli HicB Antitoxin Contains a Structurally Stable Helix-Turn-Helix DNA Binding Domain

TY - JOUR

T1 - The E. coli HicB Antitoxin Contains a Structurally Stable Helix-Turn-Helix DNA Binding Domain

AU - Manav, Melek Cemre

AU - Turnbull, Kathryn Jane

AU - Jurėnas, Dukas

AU - Garcia-Pino, Abel

AU - Gerdes, Kenn

AU - Brodersen, Ditlev Egeskov

PY - 2019

Y1 - 2019

N2 - The E. coli hicAB type II toxin-antitoxin locus is unusual by being controlled by two promoters and by having the toxin encoded upstream of the antitoxin. HicA toxins contain a double-stranded RNA-binding fold and cleaves both mRNA and tmRNA in vivo, while HicB antitoxins contain a partial RNase H fold and either a helix-turn-helix (HTH) or ribbon-helix-helix domain. It is not known how an HTH DNA-binding domain affects higher-order structure for the HicAB modules. Here, we present crystal structures of the isolated E. coli HicB antitoxin and full-length HicAB complex showing that HicB forms a stable DNA-binding module and interacts in a canonical way with HicA despite the presence of an HTH-type DNA-binding domain. No major structural rearrangements take place upon binding of the toxin. Both structures expose well-ordered DNA-binding motifs allowing a model for DNA binding by the antitoxin to be generated.

AB - The E. coli hicAB type II toxin-antitoxin locus is unusual by being controlled by two promoters and by having the toxin encoded upstream of the antitoxin. HicA toxins contain a double-stranded RNA-binding fold and cleaves both mRNA and tmRNA in vivo, while HicB antitoxins contain a partial RNase H fold and either a helix-turn-helix (HTH) or ribbon-helix-helix domain. It is not known how an HTH DNA-binding domain affects higher-order structure for the HicAB modules. Here, we present crystal structures of the isolated E. coli HicB antitoxin and full-length HicAB complex showing that HicB forms a stable DNA-binding module and interacts in a canonical way with HicA despite the presence of an HTH-type DNA-binding domain. No major structural rearrangements take place upon binding of the toxin. Both structures expose well-ordered DNA-binding motifs allowing a model for DNA binding by the antitoxin to be generated.

KW - antitoxin

KW - DNA-binding protein

KW - helix-turn-helix

KW - ribbon-helix-helix

KW - RNase H

KW - toxin

U2 - 10.1016/j.str.2019.08.008

DO - 10.1016/j.str.2019.08.008

M3 - Journal article

C2 - 31495532

AN - SCOPUS:85074171976

SN - 0969-2126

VL - 27

SP - 1675-1685, e1-e3

JO - Structure

JF - Structure

IS - 11

ER -