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Second messengers and divergent HD‐GYP phosphodiesterases regulate 3′,3′‐cGAMP signaling
Author(s) -
Wright Todd A.,
Jiang Lucy,
Park James J.,
Anderson Wyatt A.,
Chen Ge,
Hallberg Zachary F.,
Nan Beiyan,
Hammond Ming C.
Publication year - 2020
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14412
Subject(s) - second messenger system , phosphodiesterase , biology , myxococcus xanthus , activator (genetics) , microbiology and biotechnology , signal transduction , enzyme , biochemistry , gene , mutant
Summary 3′,3′‐cyclic GMP‐AMP (cGAMP) is the third cyclic dinucleotide (CDN) to be discovered in bacteria. No activators of cGAMP signaling have yet been identified, and the signaling pathways for cGAMP have been inferred to display a narrow distribution based upon the characterized synthases, DncV and Hypr GGDEFs. Here, we report that the ubiquitous second messenger cyclic AMP (cAMP) is an activator of the Hypr GGDEF enzyme GacB from Myxococcus xanthus . Furthermore, we show that GacB is inhibited directly by cyclic di‐GMP, which provides evidence for cross‐regulation between different CDN pathways. Finally, we reveal that the HD‐GYP enzyme PmxA is a cGAMP‐specific phosphodiesterase (GAP) that promotes resistance to osmotic stress in M. xanthus . A signature amino acid change in PmxA was found to reprogram substrate specificity and was applied to predict the presence of non‐canonical HD‐GYP phosphodiesterases in many bacterial species, including phyla previously not known to utilize cGAMP signaling.