TY  - JOUR
AU  - Jovanović, Goran
AU  - Sheng, Xia
AU  - Ale, Angelique
AU  - Feliu, Elisenda
AU  - Harrington, Heather A.
AU  - Kirk, Paul
AU  - Wiuf, Carsten
AU  - Buck, Martin
AU  - Stumpf, Michael P. H.
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/885
AB  - Two-component systems play a central part in bacterial signal transduction. Phosphorelay mechanisms have been linked to more robust and ultra-sensitive signalling dynamics. The molecular machinery that facilitates such a signalling is, however, only understood in outline. In particular the functional relevance of the dimerization of a non-orthodox or hybrid histidine kinase along which the phosphorelay takes place has been a subject of debate. We use a combination of molecular and genetic approaches, coupled to mathematical and statistical modelling, to demonstrate that the different possible intra- and inter-molecular mechanisms of phosphotransfer are formally non-identifiable in Escherichia coli expressing the ArcB non-orthodox histidine kinase used in anoxic redox control. In order to resolve this issue we further analyse the mathematical model in order to identify discriminatory experiments, which are then performed to address cis- and trans-phosphorelay mechanisms. The results suggest that exclusive cis- and trans-mechanisms will not be operating, instead the functional phosphorelay is likely to build around a sequence of allosteric interactions among the domain pairs in the histidine kinase. This is the first detailed mechanistic analysis of the molecular processes involved in non-orthodox two-component signalling and our results suggest strongly that dimerization facilitates more discriminatory proof-reading of external signals, via these allosteric reactions, prior to them being further processed.
PB  - Royal Soc Chemistry, Cambridge
T2  - Molecular Biosystems
T1  - Phosphorelay of non-orthodox two component systems functions through a bi-molecular mechanism in vivo: the case of ArcB
EP  - 1359
IS  - 5
SP  - 1348
VL  - 11
DO  - 10.1039/c4mb00720d
ER  - 

@article{
author = "Jovanović, Goran and Sheng, Xia and Ale, Angelique and Feliu, Elisenda and Harrington, Heather A. and Kirk, Paul and Wiuf, Carsten and Buck, Martin and Stumpf, Michael P. H.",
year = "2015",
abstract = "Two-component systems play a central part in bacterial signal transduction. Phosphorelay mechanisms have been linked to more robust and ultra-sensitive signalling dynamics. The molecular machinery that facilitates such a signalling is, however, only understood in outline. In particular the functional relevance of the dimerization of a non-orthodox or hybrid histidine kinase along which the phosphorelay takes place has been a subject of debate. We use a combination of molecular and genetic approaches, coupled to mathematical and statistical modelling, to demonstrate that the different possible intra- and inter-molecular mechanisms of phosphotransfer are formally non-identifiable in Escherichia coli expressing the ArcB non-orthodox histidine kinase used in anoxic redox control. In order to resolve this issue we further analyse the mathematical model in order to identify discriminatory experiments, which are then performed to address cis- and trans-phosphorelay mechanisms. The results suggest that exclusive cis- and trans-mechanisms will not be operating, instead the functional phosphorelay is likely to build around a sequence of allosteric interactions among the domain pairs in the histidine kinase. This is the first detailed mechanistic analysis of the molecular processes involved in non-orthodox two-component signalling and our results suggest strongly that dimerization facilitates more discriminatory proof-reading of external signals, via these allosteric reactions, prior to them being further processed.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Molecular Biosystems",
title = "Phosphorelay of non-orthodox two component systems functions through a bi-molecular mechanism in vivo: the case of ArcB",
pages = "1359-1348",
number = "5",
volume = "11",
doi = "10.1039/c4mb00720d"
}

Jovanović, G., Sheng, X., Ale, A., Feliu, E., Harrington, H. A., Kirk, P., Wiuf, C., Buck, M.,& Stumpf, M. P. H.. (2015). Phosphorelay of non-orthodox two component systems functions through a bi-molecular mechanism in vivo: the case of ArcB. in Molecular Biosystems
Royal Soc Chemistry, Cambridge., 11(5), 1348-1359.
https://doi.org/10.1039/c4mb00720d

Jovanović G, Sheng X, Ale A, Feliu E, Harrington HA, Kirk P, Wiuf C, Buck M, Stumpf MPH. Phosphorelay of non-orthodox two component systems functions through a bi-molecular mechanism in vivo: the case of ArcB. in Molecular Biosystems. 2015;11(5):1348-1359.
doi:10.1039/c4mb00720d .

Jovanović, Goran, Sheng, Xia, Ale, Angelique, Feliu, Elisenda, Harrington, Heather A., Kirk, Paul, Wiuf, Carsten, Buck, Martin, Stumpf, Michael P. H., "Phosphorelay of non-orthodox two component systems functions through a bi-molecular mechanism in vivo: the case of ArcB" in Molecular Biosystems, 11, no. 5 (2015):1348-1359,
https://doi.org/10.1039/c4mb00720d . .

TY  - JOUR
AU  - Jovanović, Goran
AU  - Mehta, Parul
AU  - Ying, Liming
AU  - Buck, Martin
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/734
AB  - All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipinrich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization.
PB  - Microbiology Soc, London
T2  - Microbiology-Sgm
T1  - Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli
EP  - 2386
SP  - 2374
VL  - 160
DO  - 10.1099/mic.0.078527-0
ER  - 

@article{
author = "Jovanović, Goran and Mehta, Parul and Ying, Liming and Buck, Martin",
year = "2014",
abstract = "All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipinrich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization.",
publisher = "Microbiology Soc, London",
journal = "Microbiology-Sgm",
title = "Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli",
pages = "2386-2374",
volume = "160",
doi = "10.1099/mic.0.078527-0"
}

Jovanović, G., Mehta, P., Ying, L.,& Buck, M.. (2014). Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli. in Microbiology-Sgm
Microbiology Soc, London., 160, 2374-2386.
https://doi.org/10.1099/mic.0.078527-0

Jovanović G, Mehta P, Ying L, Buck M. Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli. in Microbiology-Sgm. 2014;160:2374-2386.
doi:10.1099/mic.0.078527-0 .

Jovanović, Goran, Mehta, Parul, Ying, Liming, Buck, Martin, "Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli" in Microbiology-Sgm, 160 (2014):2374-2386,
https://doi.org/10.1099/mic.0.078527-0 . .