Mycobacterial STAND adenylyl cyclases: The HTH domain binds DNA to form biocrystallized nucleoids

Zaveri, Anisha; Bose, Avipsa; Sharma, Suruchi; Rajendran, Abinaya; Biswas, Priyanka; Shenoy, Avinash R.; Visweswariah, Sandhya S.

doi:10.1016/j.bpj.2020.11.008

Cited by 9 publications

(7 citation statements)

References 56 publications

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“…Expression of Rv0805, but not Rv0891c was restored in a ΔphoP -H37Rv complemented strain. Although Rv0891c has been suggested as one of the M. tuberculosis H37Rv adenylate cyclases, the protein lacks most of the important residues conserved for adenylate cyclase family of proteins (27). Conversely, Rv0805 encodes for a cAMP-specific phosphodiesterase (PDE), present only in slow growing pathogenic M. tuberculosis (28–30).…”

Section: Resultsmentioning

confidence: 99%

“…Expression of Rv0805, but not Rv0891c was restored in a phoP-H37Rv complemented strain. Although Rv0891c has been suggested as one of the M. tuberculosis H37Rv adenylate cyclases, the protein lacks most of the important residues conserved for adenylate cyclase family of proteins (27).…”

Section: Intra-mycobacterial Camp Level Is Regulated By the Phop Locusmentioning

confidence: 99%

“…Although Rv0891c was suggested as one of the M. tuberculosis H37Rv adenylate cyclases, the protein lacks most of the important residues conserved for adenylate cyclase family of proteins (Zaveri et al, 2021). On the other hand, rv0805 encodes for a cAMP specific PDE, present only in slow growing pathogenic M. tuberculosis (Matange et al, 2013;Shenoy et al, 2007;Shenoy et al, 2005).…”

Section: Phop Functions As a Repressor Of Rv0805mentioning

confidence: 99%

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Mycobacterium tuberculosisPhoP integrates stress response to intracellular survival by regulating cAMP level

Khan

Paul

Goar

et al. 2022

Preprint

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Survival of M. tuberculosis within the host macrophages requires presence of the virulence regulator PhoP, but the underlying mechanism is yet to be understood. We discovered a signalling pathway which controls mycobacterial cAMP-inducible gene expression and cAMP homeostasis. We show that the level of intra-mycobacterial cAMP, one of the most widely used second messengers, is regulated by the virulence regulator PhoP, which recruits the cAMP responsive protein, CRP. We provide evidence to show that PhoP -dependent repression of cAMP specific phosphodiesterase Rv0805, which degrades cAMP hydrolytically, accounts for mycobacterial cAMP homeostasis. In keeping with these findings, genetic manipulation to inactivate PhoP-Rv0805-cAMP pathway leads to disruption of cAMP homeostasis, increased stress sensitivity and most critically, reduced mycobacterial survival in macrophages and animal models. Together, PhoP-dependent cAMP inducible gene expression and cAMP homeostasis represent a molecular checkpoint during intra-phagosomal survival and growth program of mycobacteria.

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Section: Resultsmentioning

confidence: 99%

Section: Intra-mycobacterial Camp Level Is Regulated By the Phop Locusmentioning

confidence: 99%

Section: Phop Functions As a Repressor Of Rv0805mentioning

confidence: 99%

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Mycobacterium tuberculosisPhoP integrates stress response to intracellular survival by regulating cAMP level

Khan

Paul

Goar

et al. 2022

Preprint

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“…We did not obtain evidence showing a direct interaction of PANDA with NGR5 or its partner LC2 by yeast two-hybrid assays (data not shown). Although PANDA has HTH domain, which is a DNA-recognition motif often involved in DNA binding (Zaveri et al, 2021), PANDA did not bind to the GCC motif through the HTH domain directly (Figure S24). The results suggest that the epigenetic regulation of PANDA on the GCC motif-containing target genes, including OsMADS55 and OsEMF1, may require a yet-to-be-identified protein or protein complex.…”

Section: Discussionmentioning

confidence: 99%

The Harbinger transposon‐derived gene PANDA epigenetically coordinates panicle number and grain size in rice

Mao

Tao

et al. 2022

Plant Biotechnology Journal

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Summary Transposons significantly contribute to genome fractions in many plants. Although numerous transposon‐related mutations have been identified, the evidence regarding transposon‐derived genes regulating crop yield and other agronomic traits is very limited. In this study, we characterized a rice Harbinger transposon‐derived gene called PANICLE NUMBER AND GRAIN SIZE (PANDA), which epigenetically coordinates panicle number and grain size. Mutation of PANDA caused reduced panicle number but increased grain size in rice, while transgenic plants overexpressing this gene showed the opposite phenotypic change. The PANDA‐encoding protein can bind to the core polycomb repressive complex 2 (PRC2) components OsMSI1 and OsFIE2, and regulates the deposition of H3K27me3 in the target genes, thereby epigenetically repressing their expression. Among the target genes, both OsMADS55 and OsEMF1 were negative regulators of panicle number but positive regulators of grain size, partly explaining the involvement of PANDA in balancing panicle number and grain size. Moreover, moderate overexpression of PANDA driven by its own promoter in the indica rice cultivar can increase grain yield. Thus, our findings present a novel insight into the epigenetic control of rice yield traits by a Harbinger transposon‐derived gene and provide its potential application for rice yield improvement.

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“…Zaveri et al (6) show that a mycobacterial STAND adenylyl cyclase protein has a DNA binding helix-turn-helix domain that binds DNA and RNA nonspecifically, fused to an inactive adenylyl cyclase that nevertheless retains ATP and ADP binding. Atomic force microscopy revealed nucleotide-dependent ordering of protein-DNA complexes into solid-like higher-order structures.…”

Section: Editorialmentioning

confidence: 99%

Faces, facets, and functions of biomolecular condensates driven by multivalent proteins and nucleic acids

Kahn

Lemke

Pappu

2021

Biophysical Journal

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Mycobacterial STAND adenylyl cyclases: The HTH domain binds DNA to form biocrystallized nucleoids

Cited by 9 publications

References 56 publications

Mycobacterium tuberculosisPhoP integrates stress response to intracellular survival by regulating cAMP level

Mycobacterium tuberculosisPhoP integrates stress response to intracellular survival by regulating cAMP level

The Harbinger transposon‐derived gene PANDA epigenetically coordinates panicle number and grain size in rice

Faces, facets, and functions of biomolecular condensates driven by multivalent proteins and nucleic acids

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