YybT is a signaling protein that contains a cyclic dinucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity.
The cyclic dinucleotide c-di-AMP [corrected] synthesized by the diadenylate cyclase domain was discovered recently [corrected] as a messenger molecule for signaling DNA breaks in Bacillus subtilis. By searching bacterial genomes, we identified a family of DHH/DHHA1 domain proteins (COG3387) that co-occur with a subset of the diadenylate cyclase domain proteins. Here we report that the B. subtilis protein YybT, a member of the COG3387 family proteins, exhibits phosphodiesterase activity toward cyclic dinucleotides. The DHH/DHHA1 domain hydrolyzes c-di-AMP and c-di-GMP to generate the linear dinucleotides 5'-pApA and 5'-pGpG. The data suggest that c-di-AMP could be the physiological substrate for YybT given the physiologically relevant Michaelis-Menten constant (K(m)) and the presence of YybT family proteins in the bacteria lacking c-di-GMP signaling network. The bacterial regulator ppGpp was found to be a strong competitive inhibitor of the DHH/DHHA1 domain, suggesting that YybT is under tight control during stringent response. In addition, the atypical GGDEF domain of YybT exhibits unexpected ATPase activity, distinct from the common diguanylate cyclase activity for GGDEF domains. We further demonstrate the participation of YybT in DNA damage and acid resistance by characterizing the phenotypes of the DeltayybT mutant. The novel enzymatic activity and stress resistance together point toward a role for YybT in stress signaling and response.
Rao
Feng
F
School of Biological Sciences, Nanyang Technological University, Singapore.
See
Rui Yin
RY
Zhang
Dongwei
D
Toh
Delon Chengxu
DC
Ji
Qiang
Q
Liang
Zhao-Xun
ZX
D000143:Acids; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D004249:DNA Damage; D015226:Dinucleoside Phosphates / Q000378:metabolism; D006159:Guanosine Tetraphosphate / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D008670:Metals / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013379:Substrate Specificity / Q000187:drug effects
D000143:Acids; D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D008670:Metals; C528998:cyclic diadenosine phosphate; D006159:Guanosine Tetraphosphate; D000255:Adenosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D000251:Adenosine Triphosphatases