PMID- 34498587
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20220101
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 10
DP  - 2021 Sep 9
TI  - Structural basis for diguanylate cyclase activation by its binding partner in 
      Pseudomonas aeruginosa.
LID - 10.7554/eLife.67289 [doi]
LID - e67289
AB  - Cyclic-di-guanosine monophosphate (c-di-GMP) is an important effector associated 
      with acute-chronic infection transition in Pseudomonas aeruginosa. Previously, we 
      reported a signaling network SiaABCD, which regulates biofilm formation by 
      modulating c-di-GMP level. However, the mechanism for SiaD activation by SiaC 
      remains elusive. Here we determine the crystal structure of SiaC-SiaD-GpCpp 
      complex and revealed a unique mirror symmetric conformation: two SiaD form a 
      dimer with long stalk domains, while four SiaC bind to the conserved motifs on 
      the stalks of SiaD and stabilize the conformation for further enzymatic 
      catalysis. Furthermore, SiaD alone exhibits an inactive pentamer conformation in 
      solution, demonstrating that SiaC activates SiaD through a dynamic mechanism of 
      promoting the formation of active SiaD dimers. Mutagenesis assay confirmed that 
      the stalks of SiaD are necessary for its activation. Together, we reveal a novel 
      mechanism for DGC activation, which clarifies the regulatory networks of c-di-GMP 
      signaling.
CI  - (c) 2021, Chen et al.
FAU - Chen, Gukui
AU  - Chen G
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Zhou, Jiashen
AU  - Zhou J
AD  - Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University, 
      School of Medicine, Shanghai, China.
FAU - Zuo, Yili
AU  - Zuo Y
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Huo, Weiping
AU  - Huo W
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Peng, Juan
AU  - Peng J
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Li, Meng
AU  - Li M
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Zhang, Yani
AU  - Zhang Y
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Wang, Tietao
AU  - Wang T
AUID- ORCID: 0000-0001-8540-436X
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University, 
      School of Medicine, Shanghai, China.
FAU - Zhang, Liang
AU  - Zhang L
AUID- ORCID: 0000-0002-7672-1168
AD  - Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University, 
      School of Medicine, Shanghai, China.
FAU - Liang, Haihua
AU  - Liang H
AUID- ORCID: 0000-0001-9639-1867
AD  - Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry 
      of Education, College of Life Sciences, Northwest University, ShaanXi, China.
AD  - School of Medicine, Southern University of Science and Technology, Shenzhen, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210909
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Bacterial Proteins)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (cyclic diadenosine phosphate)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - EC 4.6.1.- (diguanylate cyclase)
SB  - IM
MH  - Bacterial Proteins/chemistry/genetics/*metabolism
MH  - Binding Sites
MH  - Biofilms/growth & development
MH  - Catalysis
MH  - Dinucleoside Phosphates/chemistry/*metabolism
MH  - Enzyme Activation
MH  - Escherichia coli Proteins/chemistry/genetics/*metabolism
MH  - Phosphorus-Oxygen Lyases/chemistry/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Pseudomonas aeruginosa/*enzymology/genetics/growth & development
MH  - Signal Transduction
MH  - Structure-Activity Relationship
PMC - PMC8457831
OTO - NOTNLM
OT  - Pseudomonas aeruginosa
OT  - SiaC
OT  - SiaD
OT  - crystal structure
OT  - infectious disease
OT  - microbiology
OT  - molecular biophysics
OT  - structural biology
COIS- GC, YZ, WH, JP, ML, YZ, TW, LZ, LZ, HL None, JZ none
EDAT- 2021/09/10 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/09/09
CRDT- 2021/09/09 08:42
PHST- 2021/02/06 00:00 [received]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/09/10 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/09/09 08:42 [entrez]
PHST- 2021/09/09 00:00 [pmc-release]
AID - 67289 [pii]
AID - 10.7554/eLife.67289 [doi]
PST - epublish
SO  - Elife. 2021 Sep 9;10:e67289. doi: 10.7554/eLife.67289.