Polyphosphate binds to the principal sigma factor of RNA polymerase during starvation response in Helicobacter pylori.
Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. Helicobacter pylori produces polyphosphate; however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively charged Lys-rich region at the N-terminal domain of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative 'region P' is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens.
Yang
Zhao Xu
ZX
National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Zhou
Yan Ning
YN
Yang
Yi
Y
Jin
Ding Jun
DJ
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011122:Polyphosphates / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012808:Sigma Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D011122:Polyphosphates; D012808:Sigma Factor; C081775:RNA polymerase sigma 70; D012321:DNA-Directed RNA Polymerases