Structural insight into the E. coli HigBA complex.
The toxin-antitoxin system is ubiquitously existed in bacteria and archaea, performing a wide variety of functions modulating cell fitness in response to environmental cues. In this report, we solved the crystal structure of the toxin-antitoxin HigBA complex from E. coli K-12 to 2.7 Å resolution. The crystal structure of the HigBA complex displays a hetero-tetramer (HigBA)2 form comprised by two HigB and two HigA subunits. Each toxin HigB resumes a microbial RNase T1 fold, characteristic of a three antiparallel β-sheet core shielded by a few α-helices at either side. Each antitoxin HigA composed of all α-helices resembles a "C"-shaped clamp nicely encompassing a HigB in the (HigBA)2 complex. Two HigA monomers dimerize at their N-terminal domain. We showed that HigA helix α1 was essential for HigA dimerization and the hetero-tetramer (HigBA)2 formation, but not for a hetero-dimeric HigBA formation. HigA dimerization mediated by helix α1 was dispensable for DNA-binding, as a heterodimeric HigBA complex still bound to the higBA operator in vitro. The HigA C-terminal domain with a helix-turn-helix fold was essential for DNA binding. We also defined two palindromes in higBA operator specifically recognized by HigA and HigBA in vitro.
School of Life Sciences, University of Dalian Science and Technology, Dalian, Liaolin Province, 230027, People's Republic of China.
Jingsi
J
Yang
Multi-disciplinary Research Center, Institute of High Energy Physics in Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Ke
K
Zhou
Multi-disciplinary Research Center, Institute of High Energy Physics in Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Peng
P
Liu
Multi-disciplinary Research Center, Institute of High Energy Physics in Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Yuhui
Y
Dong
Multi-disciplinary Research Center, Institute of High Energy Physics in Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Zengqiang
Z
Gao
School of Life Sciences, University of Dalian Science and Technology, Dalian, Liaolin Province, 230027, People's Republic of China.
Jianjun
J
Zhang
Multi-disciplinary Research Center, Institute of High Energy Physics in Chinese Academy of Sciences, Beijing, 100049, People's Republic of China. Electronic address: liuqsh@ihep.ac.cn.
Quansheng
Q
Liu
D001483:Base Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008970:Molecular Weight; D009875:Operator Regions, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C099610:HigA protein, E coli; C099611:HigB protein, E coli
HigBA; Toxin-antitoxin