Limits...
α-Hydroxyketone synthesis and sensing by Legionella and Vibrio.

Tiaden A, Hilbi H - Sensors (Basel) (2012)

Bottom Line: AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence.Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters.To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

View Article: PubMed Central - PubMed

Affiliation: Competence Center for Applied Biotechnology and Molecular Medicine, University Zürich, Zürich, Switzerland. nicki.tiaden@cabmm.uzh.ch

ABSTRACT
Bacteria synthesize and sense low molecular weight signaling molecules, termed autoinducers, to measure their population density and community complexity. One class of autoinducers, the α-hydroxyketones (AHKs), is produced and detected by the water-borne opportunistic pathogens Legionella pneumophila and Vibrio cholerae, which cause Legionnaires' disease and cholera, respectively. The "Legionella quorum sensing" (lqs) or "cholera quorum sensing" (cqs) genes encode enzymes that produce and sense the AHK molecules "Legionella autoinducer-1" (LAI-1; 3-hydroxypentadecane-4-one) or cholera autoinducer-1 (CAI-1; 3-hydroxytridecane-4-one). AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence. Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters. To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

Show MeSH

Related in: MedlinePlus

Signal transduction by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. V.chCqsS and L.pnLqsS are six trans-membrane helix sensor kinases with C-terminal cytoplasmic signal transduction domains. Predicted sub-domains (amino acids in parenthesis): HisKA (histidine kinase A domain with conserved histidine phospho-acceptor site), HATPase_c (catalytic ATP binding and transferase domain, C-terminal); REC (receiver domain with conserved aspartate). CqsS is a hybrid histidine kinase coupled to a phosphorelay system. The HisKA/HATPase_C domain catalyzes the autophosphorylation by ATP at H194 and the phosphotransfer to D618 in the REC domain. The phosphoryl group is then shuttled via the orphan phosphorelay protein LuxU (H58) to the REC domain of the response regulator LuxO (D47). In LqsS, after phosphorylation of H200, the phosphate is presumably transferred to D108 in the REC domain of the response regulator LqsR. CqsS and LqsS are likely bifunctional kinases/phosphatases.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376566&req=5

f2-sensors-12-02899: Signal transduction by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. V.chCqsS and L.pnLqsS are six trans-membrane helix sensor kinases with C-terminal cytoplasmic signal transduction domains. Predicted sub-domains (amino acids in parenthesis): HisKA (histidine kinase A domain with conserved histidine phospho-acceptor site), HATPase_c (catalytic ATP binding and transferase domain, C-terminal); REC (receiver domain with conserved aspartate). CqsS is a hybrid histidine kinase coupled to a phosphorelay system. The HisKA/HATPase_C domain catalyzes the autophosphorylation by ATP at H194 and the phosphotransfer to D618 in the REC domain. The phosphoryl group is then shuttled via the orphan phosphorelay protein LuxU (H58) to the REC domain of the response regulator LuxO (D47). In LqsS, after phosphorylation of H200, the phosphate is presumably transferred to D108 in the REC domain of the response regulator LqsR. CqsS and LqsS are likely bifunctional kinases/phosphatases.

Mentions: A common feature of the sensor histidine kinases CqsS, LuxQ and LuxN is their ability to switch between kinase and phosphatase function. The LuxQ [75] and LuxN [76] sensor kinases have been instrumental to study mechanistic aspects of coupling the binding of an AI ligand to the switch from kinase to phosphatase activity. High-resolution crystal structures of the periplasmic binding protein LuxP and a fragment of the sensor kinase LuxQ in complex with or without its ligand AI-2 revealed that binding of AI-2 to LuxP disrupts tetrameric complexes of LuxPQ dimers, thus causing a switch from kinase to phosphatase activity. Similarly, a switch from kinase to phosphatase activity is also proposed for CqsS upon interaction with its ligand CAI-1 (Figure 2). However, the exact mechanism of how CAI-1 binding alters the oligomerization state and the activity of a putative CqsS dimer has to be elucidated. At low AI concentration the sensor kinase activity will lead to phosphorylation and activation of the downstream targets LuxU and LuxO. Conversely, at high AI concentration the sensor phosphorylation activity will result in the dephosphorylation and inactivation of LuxU and LuxO.


α-Hydroxyketone synthesis and sensing by Legionella and Vibrio.

Tiaden A, Hilbi H - Sensors (Basel) (2012)

Signal transduction by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. V.chCqsS and L.pnLqsS are six trans-membrane helix sensor kinases with C-terminal cytoplasmic signal transduction domains. Predicted sub-domains (amino acids in parenthesis): HisKA (histidine kinase A domain with conserved histidine phospho-acceptor site), HATPase_c (catalytic ATP binding and transferase domain, C-terminal); REC (receiver domain with conserved aspartate). CqsS is a hybrid histidine kinase coupled to a phosphorelay system. The HisKA/HATPase_C domain catalyzes the autophosphorylation by ATP at H194 and the phosphotransfer to D618 in the REC domain. The phosphoryl group is then shuttled via the orphan phosphorelay protein LuxU (H58) to the REC domain of the response regulator LuxO (D47). In LqsS, after phosphorylation of H200, the phosphate is presumably transferred to D108 in the REC domain of the response regulator LqsR. CqsS and LqsS are likely bifunctional kinases/phosphatases.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376566&req=5

f2-sensors-12-02899: Signal transduction by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. V.chCqsS and L.pnLqsS are six trans-membrane helix sensor kinases with C-terminal cytoplasmic signal transduction domains. Predicted sub-domains (amino acids in parenthesis): HisKA (histidine kinase A domain with conserved histidine phospho-acceptor site), HATPase_c (catalytic ATP binding and transferase domain, C-terminal); REC (receiver domain with conserved aspartate). CqsS is a hybrid histidine kinase coupled to a phosphorelay system. The HisKA/HATPase_C domain catalyzes the autophosphorylation by ATP at H194 and the phosphotransfer to D618 in the REC domain. The phosphoryl group is then shuttled via the orphan phosphorelay protein LuxU (H58) to the REC domain of the response regulator LuxO (D47). In LqsS, after phosphorylation of H200, the phosphate is presumably transferred to D108 in the REC domain of the response regulator LqsR. CqsS and LqsS are likely bifunctional kinases/phosphatases.
Mentions: A common feature of the sensor histidine kinases CqsS, LuxQ and LuxN is their ability to switch between kinase and phosphatase function. The LuxQ [75] and LuxN [76] sensor kinases have been instrumental to study mechanistic aspects of coupling the binding of an AI ligand to the switch from kinase to phosphatase activity. High-resolution crystal structures of the periplasmic binding protein LuxP and a fragment of the sensor kinase LuxQ in complex with or without its ligand AI-2 revealed that binding of AI-2 to LuxP disrupts tetrameric complexes of LuxPQ dimers, thus causing a switch from kinase to phosphatase activity. Similarly, a switch from kinase to phosphatase activity is also proposed for CqsS upon interaction with its ligand CAI-1 (Figure 2). However, the exact mechanism of how CAI-1 binding alters the oligomerization state and the activity of a putative CqsS dimer has to be elucidated. At low AI concentration the sensor kinase activity will lead to phosphorylation and activation of the downstream targets LuxU and LuxO. Conversely, at high AI concentration the sensor phosphorylation activity will result in the dephosphorylation and inactivation of LuxU and LuxO.

Bottom Line: AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence.Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters.To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

View Article: PubMed Central - PubMed

Affiliation: Competence Center for Applied Biotechnology and Molecular Medicine, University Zürich, Zürich, Switzerland. nicki.tiaden@cabmm.uzh.ch

ABSTRACT
Bacteria synthesize and sense low molecular weight signaling molecules, termed autoinducers, to measure their population density and community complexity. One class of autoinducers, the α-hydroxyketones (AHKs), is produced and detected by the water-borne opportunistic pathogens Legionella pneumophila and Vibrio cholerae, which cause Legionnaires' disease and cholera, respectively. The "Legionella quorum sensing" (lqs) or "cholera quorum sensing" (cqs) genes encode enzymes that produce and sense the AHK molecules "Legionella autoinducer-1" (LAI-1; 3-hydroxypentadecane-4-one) or cholera autoinducer-1 (CAI-1; 3-hydroxytridecane-4-one). AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence. Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters. To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

Show MeSH
Related in: MedlinePlus