Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.2 (
guanylate cyclase
)
8,497
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
cGMP signaling is one of the master regulators of diverse functions in eukaryotes; however, its architecture and functioning in protozoans remain poorly understood. Herein, we report an exclusive
guanylate cyclase
coupled with N-terminal P4-ATPase in a common parasitic protist,
Toxoplasma gondii
This bulky protein (477-kD), termed
Tg
ATPase
P
-GC to fairly reflect its envisaged multifunctionality, localizes in the plasma membrane at the apical pole of the parasite, whereas the corresponding cGMP-dependent protein kinase (
Tg
PKG) is distributed in the cytomembranes.
Tg
ATPase
P
-GC is refractory to genetic deletion, and its CRISPR/Cas9-assisted disruption aborts the lytic cycle of
T. gondii
Besides, Cre/loxP-mediated knockdown of
Tg
ATPase
P
-GC reduced the synthesis of cGMP and inhibited the parasite growth due to impairments in the motility-dependent egress and invasion events. Equally, repression of
Tg
PKG by a similar strategy recapitulated phenotypes of the
Tg
ATPase
P
-GC-depleted mutant. Notably, despite a temporally restricted function,
Tg
ATPase
P
-GC is expressed constitutively throughout the lytic cycle, entailing a post-translational regulation of cGMP signaling. Not least, the occurrence of
Tg
ATPase
P
-GC orthologs in several other alveolates implies a divergent functional repurposing of cGMP signaling in protozoans, and offers an excellent drug target against the parasitic protists.
Life Sci
Alliance
2019 06
PMID:An unusual and vital protein with guanylate cyclase and P4-ATPase domains in a pathogenic protist. 3123 76
