PXD032173
PXD032173 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mutagenesis of Key Phosphodiesterases in Toxoplasma gondii Demonstrates the Plasticity and Therapeutic Potential of Cyclic Nucleotide Signaling |
Description | Cyclic nucleotide signaling is pivotal to the asexual growth of T. gondii; however, little do we know about its counter-regulation in this parasite. We identified 18 phosphodiesterase (PDE1-18) enzymes, most of which form apicomplexan-specific clades and lack typical regulatory motifs found in mammalian PDEs. Genomic epitope-tagging in the tachyzoite stage showed the variable expression of 11 phosphodiesterases with diverse subcellular distribution. Most PDEs can degrade cAMP as well as cGMP with different affinity except for PDE2 which is cAMP-specific. In our extended work, we examined PDE1,2,7-9 for their physiological importance during the lytic cycle. Surprisingly, tachyzoites can tolerate the deletion of PDE1, 7-9 genes with no apparent impairment of the lytic cycle, suggesting remarkable plasticity in the cyclic nucleotide signaling. Co-ablation of PDE1 and PDE2 is detrimental to the parasite growth due to impairment of motility, invasion, egress and replication. The immunogold transmission electron microscopy revealed TgPDE1,2 in the cytomembranes including the inner membrane complex. Not least, we identified a number of proteins that interact with PDE1 and PDE2 and thereby regulate cAMP/cGMP signaling in tachyzoites. In summary, our work lays a strong foundation to decipher the mechanism of cyclic nucleotide signaling and exploit it for therapeutic inhibition of T. gondii. |
HostingRepository | jPOST |
AnnounceDate | 2023-02-22 |
AnnouncementXML | Submission_2023-02-23_23:21:28.119.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ute Distler |
SpeciesList | scientific name: cellular organisms; NCBI TaxID: 131567; |
ModificationList | S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide |
Instrument | instrument |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-03-09 05:08:04 | ID requested | |
1 | 2023-02-21 08:03:26 | announced | |
⏵ 2 | 2023-02-23 23:21:28 | announced | 2023-02-24: Updated PubMed. |
Publication List
Vo KC, Ruga L, Psathaki OE, Franzkoch R, Distler U, Tenzer S, Hensel M, Hegemann P, Gupta N, . Comput Struct Biotechnol J, 20():5775-5789(2022) [pubmed] |
Keyword List
submitter keyword: Toxoplasma gondii, phosphodiesterase, PDE1, PDE2, immunoprecipitation |
Contact List
Stefan Tenzer | |
---|---|
lab head | |
Ute Distler | |
contact affiliation | University Medical Center Mainz |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST001521/ |