PMID- 34475207
OWN - NLM
STAT- MEDLINE
DCOM- 20220104
LR  - 20240403
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 118
IP  - 36
DP  - 2021 Sep 7
TI  - Differential ligand-selective control of opposing enzymatic activities within a 
      bifunctional c-di-GMP enzyme.
LID - 10.1073/pnas.2100657118 [doi]
LID - e2100657118
AB  - Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a second messenger 
      that modulates bacterial cellular processes, including biofilm formation. While 
      proteins containing both c-di-GMP synthesizing (GGDEF) and c-di-GMP hydrolyzing 
      (EAL) domains are widely predicted in bacterial genomes, it is poorly understood 
      how domains with opposing enzymatic activity are regulated within a single 
      polypeptide. Herein, we report the characterization of a globin-coupled sensor 
      protein (GCS) from Paenibacillus dendritiformis (DcpG) with bifunctional c-di-GMP 
      enzymatic activity. DcpG contains a regulatory sensor globin domain linked to 
      diguanylate cyclase (GGDEF) and phosphodiesterase (EAL) domains that are 
      differentially regulated by gas binding to the heme; GGDEF domain activity is 
      activated by the Fe(II)-NO state of the globin domain, while EAL domain activity 
      is activated by the Fe(II)-O(2) state. The in vitro activity of DcpG is mimicked 
      in vivo by the biofilm formation of P. dendritiformis in response to gaseous 
      environment, with nitric oxide conditions leading to the greatest amount of 
      biofilm formation. The ability of DcpG to differentially control GGDEF and EAL 
      domain activity in response to ligand binding is likely due to the unusual 
      properties of the globin domain, including rapid ligand dissociation rates and 
      high midpoint potentials. Using structural information from small-angle X-ray 
      scattering and negative stain electron microscopy studies, we developed a 
      structural model of DcpG, providing information about the regulatory mechanism. 
      These studies provide information about full-length GCS protein architecture and 
      insight into the mechanism by which a single regulatory domain can selectively 
      control output domains with opposing enzymatic activities.
FAU - Patterson, Dayna C
AU  - Patterson DC
AUID- ORCID: 0000-0003-1950-0331
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802.
FAU - Ruiz, Myrrh Perez
AU  - Ruiz MP
AUID- ORCID: 0000-0003-3620-8738
AD  - Department of Biochemistry and Molecular Biology, The Pennsylvania State 
      University, University Park, PA 16802.
FAU - Yoon, Hyerin
AU  - Yoon H
AD  - Department of Chemistry, Emory University, Atlanta, GA 30322.
FAU - Walker, Johnnie A
AU  - Walker JA
AD  - Department of Chemistry, Emory University, Atlanta, GA 30322.
FAU - Armache, Jean-Paul
AU  - Armache JP
AUID- ORCID: 0000-0001-9195-2282
AD  - Department of Biochemistry and Molecular Biology, The Pennsylvania State 
      University, University Park, PA 16802.
AD  - The Huck Institutes of the Life Sciences, The Pennsylvania State University, 
      University Park, PA 16802.
FAU - Yennawar, Neela H
AU  - Yennawar NH
AUID- ORCID: 0000-0001-7278-659X
AD  - The Huck Institutes of the Life Sciences, The Pennsylvania State University, 
      University Park, PA 16802.
FAU - Weinert, Emily E
AU  - Weinert EE
AUID- ORCID: 0000-0002-4986-8682
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802; emily.weinert@psu.edu.
AD  - Department of Biochemistry and Molecular Biology, The Pennsylvania State 
      University, University Park, PA 16802.
AD  - The Huck Institutes of the Life Sciences, The Pennsylvania State University, 
      University Park, PA 16802.
LA  - eng
GR  - P30 GM124166/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bacterial Proteins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Ligands)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - EC 4.6.1.- (diguanylate cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - Paenibacillus dendritiformis
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Bacterial Proteins/metabolism
MH  - Biofilms/growth & development
MH  - Cyclic GMP/*metabolism
MH  - Escherichia coli Proteins/genetics/*metabolism
MH  - Gene Expression/genetics
MH  - Gene Expression Regulation, Bacterial/genetics
MH  - Ligands
MH  - Paenibacillus/*enzymology/metabolism
MH  - Phosphoric Diester Hydrolases/metabolism
MH  - Phosphorus-Oxygen Lyases/genetics/*metabolism
MH  - Protein Domains/genetics
MH  - Second Messenger Systems/genetics
PMC - PMC8433548
OTO - NOTNLM
OT  - bifunctional enzyme
OT  - cyclic di-GMP
OT  - heme sensor
COIS- The authors declare no competing interest.
EDAT- 2021/09/04 06:00
MHDA- 2022/01/05 06:00
PMCR- 2022/03/02
CRDT- 2021/09/03 05:58
PHST- 2021/08/02 00:00 [accepted]
PHST- 2021/08/06 00:00 [received]
PHST- 2021/09/03 05:58 [entrez]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2022/01/05 06:00 [medline]
PHST- 2022/03/02 00:00 [pmc-release]
AID - 2100657118 [pii]
AID - 202100657 [pii]
AID - 10.1073/pnas.2100657118 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2100657118. doi: 
      10.1073/pnas.2100657118.