5z7c

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crystal structure of cyclic GMP-AMP specifc phosphodiesterases in V.cholerae (V-cGAP3)

Structural highlights

5z7c is a 1 chain structure with sequence from Vibrio cholerae O1 biovar El Tor str. N16961. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.76Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CGAP3_VIBCH Phosphodiesterase (PDE) that catalyzes the hydrolysis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG. Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP.^[1]

Publication Abstract from PubMed

3'3'-cyclic GMP-AMP (3'3'-cGAMP) belongs to a family of the bacterial secondary messenger cyclic dinucleotides. It was first discovered in the Vibrio cholerae seventh pandemic strains and is involved in efficient intestinal colonization and chemotaxis regulation. Phosphodiesterases (PDEs) that degrade 3'3'-cGAMP play important regulatory roles in the relevant signaling pathways, and a previous study has identified three PDEs in V. cholerae, namely, V-cGAP1, V-cGAP2, and V-cGAP3, functioning in 3'3'-cGAMP degradation. We report the crystal structure, biochemical, and structural analyses of V-cGAP3, providing a foundation for understanding the mechanism of 3'3'-cGAMP degradation and regulation in general. Our crystal and molecular dynamic (MD)-simulated structures revealed that V-cGAP3 contains tandem HD-GYP domains within its N- and C-terminal domains, with similar three-dimensional topologies despite their low-sequence identity. Biochemical and structural analyses showed that the N-terminal domain plays a mechanism of positive regulation for the catalytic C-terminal domain. We also demonstrated that the other homologous Vibrio PDEs, V-cGAP1/2, likely function via a similar mechanism.

Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3.,Deng MJ, Tao J, E C, Ye ZY, Jiang Z, Yu J, Su XD J Mol Biol. 2018 Dec 7;430(24):5080-5093. doi: 10.1016/j.jmb.2018.10.010. Epub, 2018 Oct 24. PMID:30365951^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gao J, Tao J, Liang W, Zhao M, Du X, Cui S, Duan H, Kan B, Su X, Jiang Z. Identification and characterization of phosphodiesterases that specifically degrade 3'3'-cyclic GMP-AMP. Cell Res. 2015 May;25(5):539-50. doi: 10.1038/cr.2015.40. Epub 2015 Apr 3. PMID:25837739 doi:http://dx.doi.org/10.1038/cr.2015.40
↑ Deng MJ, Tao J, E C, Ye ZY, Jiang Z, Yu J, Su XD. Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3. J Mol Biol. 2018 Dec 7;430(24):5080-5093. doi: 10.1016/j.jmb.2018.10.010. Epub, 2018 Oct 24. PMID:30365951 doi:http://dx.doi.org/10.1016/j.jmb.2018.10.010