Second messengers and divergent HD‐GYP phosphodiesterases regulate 3′,3′‐cGAMP signaling
Second messengers and divergent HD‐GYP phosphodiesterases regulate 3′,3′‐cGAMP signaling
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DOI：
10.1111/mmi.14412
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发表时间：
2020-01
影响因子：
3.6
通讯作者：
Todd A. Wright;Lucy Jiang;James J. Park;W. A. Anderson;Ge Chen;Zachary F. Hallberg;Beiyan Nan;M. C. Hammond
中科院分区：
文献类型：
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作者：
Todd A. Wright;Lucy Jiang;James J. Park;W. A. Anderson;Ge Chen;Zachary F. Hallberg;Beiyan Nan;M. C. Hammond
3′，3 ′-环GMP-AMP（cGAMP）是在细菌中发现的第三种环二核苷酸（CDN）。尚未鉴定出cGAMP信号传导的活化剂，并且基于表征的双磷酸酶、DncV和Hypr GGDEF，推断cGAMP的信号传导途径显示窄分布。在这里，我们报告说，无处不在的第二信使环腺苷酸（cAMP）是一个激活剂的Hypr GGDEF酶GacB从粘球菌黄。此外，我们表明GacB直接被环二GMP抑制，这为不同CDN途径之间的交叉调节提供了证据。最后，我们揭示了HD-GYP酶PmxA是一种cGAMP特异性磷酸二酯酶（GAP），可促进M. xanthus发现PmxA中的标志性氨基酸变化重新编程底物特异性，并应用于预测许多细菌物种中非经典HD-GYP磷酸二酯酶的存在，包括以前不知道利用cGAMP信号传导的门。
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.