Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase.

Research output: Contribution to journalArticle

Standard

Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase. / Cadby, Ian T; Basford, Sarah M ; Nottingham, Ruth ; Meek, Richard; Lowry, Rebecca ; Lambert, Carey; Tridgett, Matthew; Till, Rob; Ahmad, Rashidah ; Fung, Rowena ; Hobley, Laura ; Hughes, William S; Moynihan, Patrick J; Sockett, R. Elizabeth; Lovering, Andrew.

In: The EMBO journal, Vol. 38, No. 15, e100772, 29.07.2019.

Research output: Contribution to journalArticle

Harvard

Cadby, IT, Basford, SM, Nottingham, R, Meek, R, Lowry, R, Lambert, C, Tridgett, M, Till, R, Ahmad, R, Fung, R, Hobley, L, Hughes, WS, Moynihan, PJ, Sockett, RE & Lovering, A 2019, 'Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase.', The EMBO journal, vol. 38, no. 15, e100772. https://doi.org/10.15252/embj.2018100772

APA

Cadby, I. T., Basford, S. M., Nottingham, R., Meek, R., Lowry, R., Lambert, C., Tridgett, M., Till, R., Ahmad, R., Fung, R., Hobley, L., Hughes, W. S., Moynihan, P. J., Sockett, R. E., & Lovering, A. (2019). Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase. The EMBO journal, 38(15), [e100772]. https://doi.org/10.15252/embj.2018100772

Vancouver

Author

Cadby, Ian T ; Basford, Sarah M ; Nottingham, Ruth ; Meek, Richard ; Lowry, Rebecca ; Lambert, Carey ; Tridgett, Matthew ; Till, Rob ; Ahmad, Rashidah ; Fung, Rowena ; Hobley, Laura ; Hughes, William S ; Moynihan, Patrick J ; Sockett, R. Elizabeth ; Lovering, Andrew. / Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase. In: The EMBO journal. 2019 ; Vol. 38, No. 15.

Bibtex

@article{794ca14e924c4a9eac8a514dbbb221ae,
title = "Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase.",
abstract = "Bacterial usage of the cyclic dinucleotide c-di-GMP is widespread, governing the transition between motile/sessile and unicellular/multicellular behaviors. There is limited information on c-di-GMP metabolism, particularly on regulatory mechanisms governing control of EAL c-di-GMP phosphodiesterases. Herein, we provide high-resolution structures for an EAL enzyme Bd1971, from the predatory bacterium Bdellovibrio bacteriovorus, which is controlled by a second signaling nucleotide, cAMP. The full-length cAMP-bound form reveals the sensory N-terminus to be a domain-swapped variant of the cNMP/CRP family, which in the cAMP-activated state holds the C-terminal EAL enzyme in a phosphodiesterase-active conformation. Using a truncation mutant, we trap both a half-occupied and inactive apo-form of the protein, demonstrating a series of conformational changes that alter juxtaposition of the sensory domains. We show that Bd1971 interacts with several GGDEF proteins (c-di-GMP producers), but mutants of Bd1971 do not share the discrete phenotypes of GGDEF mutants, instead having an elevated level of c-di-GMP, suggesting that the role of Bd1971 is to moderate these levels, allowing {"}action potentials{"} to be generated by each GGDEF protein to effect their specific functions.",
keywords = "bacterial signaling, Bdellovibrio, cAMP, Cyclic-di-GMP, EAL domain",
author = "Cadby, {Ian T} and Basford, {Sarah M} and Ruth Nottingham and Richard Meek and Rebecca Lowry and Carey Lambert and Matthew Tridgett and Rob Till and Rashidah Ahmad and Rowena Fung and Laura Hobley and Hughes, {William S} and Moynihan, {Patrick J} and Sockett, {R. Elizabeth} and Andrew Lovering",
note = "{\textcopyright} 2019 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2019",
month = jul
day = "29",
doi = "10.15252/embj.2018100772",
language = "English",
volume = "38",
journal = "The EMBO journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "15",

}

RIS

TY - JOUR

T1 - Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase.

AU - Cadby, Ian T

AU - Basford, Sarah M

AU - Nottingham, Ruth

AU - Meek, Richard

AU - Lowry, Rebecca

AU - Lambert, Carey

AU - Tridgett, Matthew

AU - Till, Rob

AU - Ahmad, Rashidah

AU - Fung, Rowena

AU - Hobley, Laura

AU - Hughes, William S

AU - Moynihan, Patrick J

AU - Sockett, R. Elizabeth

AU - Lovering, Andrew

N1 - © 2019 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2019/7/29

Y1 - 2019/7/29

N2 - Bacterial usage of the cyclic dinucleotide c-di-GMP is widespread, governing the transition between motile/sessile and unicellular/multicellular behaviors. There is limited information on c-di-GMP metabolism, particularly on regulatory mechanisms governing control of EAL c-di-GMP phosphodiesterases. Herein, we provide high-resolution structures for an EAL enzyme Bd1971, from the predatory bacterium Bdellovibrio bacteriovorus, which is controlled by a second signaling nucleotide, cAMP. The full-length cAMP-bound form reveals the sensory N-terminus to be a domain-swapped variant of the cNMP/CRP family, which in the cAMP-activated state holds the C-terminal EAL enzyme in a phosphodiesterase-active conformation. Using a truncation mutant, we trap both a half-occupied and inactive apo-form of the protein, demonstrating a series of conformational changes that alter juxtaposition of the sensory domains. We show that Bd1971 interacts with several GGDEF proteins (c-di-GMP producers), but mutants of Bd1971 do not share the discrete phenotypes of GGDEF mutants, instead having an elevated level of c-di-GMP, suggesting that the role of Bd1971 is to moderate these levels, allowing "action potentials" to be generated by each GGDEF protein to effect their specific functions.

AB - Bacterial usage of the cyclic dinucleotide c-di-GMP is widespread, governing the transition between motile/sessile and unicellular/multicellular behaviors. There is limited information on c-di-GMP metabolism, particularly on regulatory mechanisms governing control of EAL c-di-GMP phosphodiesterases. Herein, we provide high-resolution structures for an EAL enzyme Bd1971, from the predatory bacterium Bdellovibrio bacteriovorus, which is controlled by a second signaling nucleotide, cAMP. The full-length cAMP-bound form reveals the sensory N-terminus to be a domain-swapped variant of the cNMP/CRP family, which in the cAMP-activated state holds the C-terminal EAL enzyme in a phosphodiesterase-active conformation. Using a truncation mutant, we trap both a half-occupied and inactive apo-form of the protein, demonstrating a series of conformational changes that alter juxtaposition of the sensory domains. We show that Bd1971 interacts with several GGDEF proteins (c-di-GMP producers), but mutants of Bd1971 do not share the discrete phenotypes of GGDEF mutants, instead having an elevated level of c-di-GMP, suggesting that the role of Bd1971 is to moderate these levels, allowing "action potentials" to be generated by each GGDEF protein to effect their specific functions.

KW - bacterial signaling

KW - Bdellovibrio

KW - cAMP

KW - Cyclic-di-GMP

KW - EAL domain

UR - https://doi.org/10.15252/embj.2018100772

U2 - 10.15252/embj.2018100772

DO - 10.15252/embj.2018100772

M3 - Article

C2 - 31355487

VL - 38

JO - The EMBO journal

JF - The EMBO journal

SN - 0261-4189

IS - 15

M1 - e100772

ER -