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A pGpG-specific phosphodiesterase regulates cyclic di-GMP signaling in Vibrio cholerae.
| Content Provider | Europe PMC |
|---|---|
| Author | Heo, Kyoo Lee, Jae-Woo Jang, Yongdae Kwon, Sohee Lee, Jaehun Seok, Chaok Ha, Nam-Chul Seok, Yeong-Jae |
| Copyright Year | 2022 |
| Abstract | The bacterial second messenger bis-(3′-5′)-cyclic diguanylate monophosphate (c-di-GMP) controls various cellular processes, including motility, toxin production, and biofilm formation. c-di-GMP is enzymatically synthesized by GGDEF domain–containing diguanylate cyclases and degraded by HD-GYP domain–containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain–containing PDE-As to 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine (pGpG). Since excess pGpG feedback inhibits PDE-A activity and thereby can lead to the uncontrolled accumulation of c-di-GMP, a PDE that degrades pGpG to 2 GMP (PDE-B) has been presumed to exist. To date, the only enzyme known to hydrolyze pGpG is oligoribonuclease Orn, which degrades all kinds of oligoribonucleotides. Here, we identified a pGpG-specific PDE, which we named PggH, using biochemical approaches in the gram-negative bacteria Vibrio cholerae. Biochemical experiments revealed that PggH exhibited specific PDE activity only toward pGpG, thus differing from the previously reported Orn. Furthermore, the high-resolution structure of PggH revealed the basis for its PDE activity and narrow substrate specificity. Finally, we propose that PggH could modulate the activities of PDE-As and the intracellular concentration of c-di-GMP, resulting in phenotypic changes including in biofilm formation. |
| ISSN | 00219258 |
| Volume Number | 298 |
| PubMed Central reference number | PMC8861645 |
| Issue Number | 3 |
| PubMed reference number | 35074425 |
| Journal | The Journal of Biological Chemistry [J. Biol. Chem] |
| e-ISSN | 1083351X |
| DOI | 10.1016/j.jbc.2022.101626 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2022-01-21 |
| Access Restriction | Open |
| Rights License | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). © 2022 The Authors |
| Subject Keyword | cyclic di-GMP biofilm phosphodiesterases virulence factor enzyme kinetics c-di-GMP, bis-(3′-5′)-cyclic diguanylate monophosphate ITC, isothermal titration calorimetry PDE, phosphodiesterase pGpG, 5ʹ-phosphoguanylyl-(3ʹ,5ʹ)-guanosine PggH, phosphoguanylyl guanylate hydrolase |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry |
