PMID- 33097692
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20210803
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Oct 23
TI  - The nucleotide pGpp acts as a third alarmone in Bacillus, with functions distinct 
      from those of (p) ppGpp.
PG  - 5388
LID - 10.1038/s41467-020-19166-1 [doi]
LID - 5388
AB  - The alarmone nucleotides guanosine tetraphosphate and pentaphosphate, commonly 
      referred to as (p)ppGpp, regulate bacterial responses to nutritional and other 
      stresses. There is evidence for potential existence of a third alarmone, 
      guanosine-5'-monophosphate-3'-diphosphate (pGpp), with less-clear functions. 
      Here, we demonstrate the presence of pGpp in bacterial cells, and perform a 
      comprehensive screening to identify proteins that interact respectively with 
      pGpp, ppGpp and pppGpp in Bacillus species. Both ppGpp and pppGpp interact with 
      proteins involved in inhibition of purine nucleotide biosynthesis and with 
      GTPases that control ribosome assembly or activity. By contrast, pGpp interacts 
      with purine biosynthesis proteins but not with the GTPases. In addition, we show 
      that hydrolase NahA (also known as YvcI) efficiently produces pGpp by hydrolyzing 
      (p)ppGpp, thus modulating alarmone composition and function. Deletion of nahA 
      leads to reduction of pGpp levels, increased (p)ppGpp levels, slower growth 
      recovery from nutrient downshift, and loss of competitive fitness. Our results 
      support the existence and physiological relevance of pGpp as a third alarmone, 
      with functions that can be distinct from those of (p)ppGpp.
FAU - Yang, Jin
AU  - Yang J
AUID- ORCID: 0000-0003-3442-5608
AD  - Department of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
FAU - Anderson, Brent W
AU  - Anderson BW
AUID- ORCID: 0000-0003-2785-5343
AD  - Department of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
FAU - Turdiev, Asan
AU  - Turdiev A
AD  - Department of Cell Biology and Molecular Genetics, University of Maryland, 
      College Park, MD, USA.
FAU - Turdiev, Husan
AU  - Turdiev H
AD  - Department of Cell Biology and Molecular Genetics, University of Maryland, 
      College Park, MD, USA.
FAU - Stevenson, David M
AU  - Stevenson DM
AD  - Department of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
FAU - Amador-Noguez, Daniel
AU  - Amador-Noguez D
AUID- ORCID: 0000-0002-3568-3070
AD  - Department of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA.
FAU - Lee, Vincent T
AU  - Lee VT
AUID- ORCID: 0000-0002-3593-0318
AD  - Department of Cell Biology and Molecular Genetics, University of Maryland, 
      College Park, MD, USA. vtlee@umd.edu.
FAU - Wang, Jue D
AU  - Wang JD
AUID- ORCID: 0000-0003-1503-170X
AD  - Department of Bacteriology, University of Wisconsin, Madison, WI, 53706, USA. 
      wang@bact.wisc.edu.
LA  - eng
GR  - R01 AI110740/AI/NIAID NIH HHS/United States
GR  - R35 GM127088/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201023
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Bacterial Proteins)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nucleotides)
RN  - 33503-72-9 (Guanosine Tetraphosphate)
RN  - 58902-76-4 (guanosine 5'-diphosphate-3'-monophosphate)
SB  - IM
EIN - Nat Commun. 2021 Jun 16;12(1):3857. PMID: 34135343
MH  - Bacillus/genetics/*metabolism
MH  - Bacillus anthracis/metabolism
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Gene Expression Regulation, Bacterial
MH  - Guanine Nucleotides/*metabolism
MH  - Guanosine Tetraphosphate/metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Nucleotides/*metabolism
MH  - Protein Binding
MH  - Protein Biosynthesis
PMC - PMC7584652
COIS- The authors declare no competing interests.
EDAT- 2020/10/25 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/10/23
CRDT- 2020/10/24 05:29
PHST- 2020/05/05 00:00 [received]
PHST- 2020/09/23 00:00 [accepted]
PHST- 2020/10/24 05:29 [entrez]
PHST- 2020/10/25 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/10/23 00:00 [pmc-release]
AID - 10.1038/s41467-020-19166-1 [pii]
AID - 19166 [pii]
AID - 10.1038/s41467-020-19166-1 [doi]
PST - epublish
SO  - Nat Commun. 2020 Oct 23;11(1):5388. doi: 10.1038/s41467-020-19166-1.