Differential processing of quorum sensing signals through phosphotransfer: structural insights from molecular dynamics simulations

  • Devlina Chakravarty
  • Pinak ChakrabartiEmail author
  • Mousumi BanerjeeEmail author
Original Article


The auto-inducer-mediated virulence gene expression and biofilm formation in Vibrio sp. uses a highly evolved two-component phosphotransfer system, involving a histidine sensor kinase (LuxQ), an Hpt domain protein (LuxU) and a universal response regulator (LuxO), to process the signal. At low and high cell density, the phosphotransfer reaction occurs differently leading to the activation or deactivation, respectively, of the global repressor which in turn regulates the virulence. Here the molecular details of signal processing and signal decay have been studied using structural modelling and molecular dynamics simulation of LuxQ, LuxU and LuxO individual proteins and protein–protein complexes with and without the phosphate group. The stability, conformational flexibility and structural changes associated with phosphotransfer of the individual protein and the protein–protein complexes are compared. The root mean square deviations and the root mean square fluctuations of the phosphorylated and unphosphorylated proteins showed significant differences in these two processes. The principal component analysis points out the remarkable differences in the essential motions of the systems, which depend not only on the phosphorylated complex but also on the key phosphorylation of the individual protein component. This observation is also highlighted by the dynamic cross-correlation matrix (DCCM) analysis where concerted motions are found to differ depending on the state of phosphorylation. Evaluation of the equilibrated structures and their free energy reveals that the reverse transfer of phosphate during signal decay is energetically less favourable.


Vibrio harveyi Quorum sensing Auto-inducer Signalling pathway proteins Molecular dynamics simulation 



Molecular dynamics


Protein Data Bank


Nuclear magnetic resonance


Generalized Born solvent accessible surface area


Root mean square deviation


Root mean square fluctuation


Dynamic cross-correlation map


Principal component analysis



Our sincere thanks to Drs. Soumalee Basu and Shaon Roy Choudhuri (Maulana Abul Kalam Azad University of Technology) for their helpful discussion. MB thanks UGC, India, for D. S Kothari post-doctoral fellowship and Dr. Raju Mukherjee for a critical reading of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

Supplementary material

42485_2019_10_MOESM1_ESM.docx (3.5 mb)
Supplementary material 1 (DOCX 3552 kb)
42485_2019_10_MOESM2_ESM.mpg (5.6 mb)
Supplementary material 2 (MPG 5698 kb) SM1. Dynamics of unphosphorylated LuxUQ. LuxU is shown in green and LuxQ in blue cartoons, active site residues His58 in blue and Asp107 in red sticks
42485_2019_10_MOESM3_ESM.mpg (6 mb)
Supplementary material 3 (MPG 6170 kb) SM2. Dynamics of LuxUQ with phosphorylated Asp107
42485_2019_10_MOESM4_ESM.mpg (5.2 mb)
Supplementary material 4 (MPG 5306 kb) SM3. Dynamics of LuxUQ with phosphorylated His58
42485_2019_10_MOESM5_ESM.jpg (55 kb)
Supplementary material 5 (JPEG 54 kb) SM4. The motion captured by PC1 in unphosphorylated LuxUQ. The protein is shown as ribbon (LuxQ in blue). The helices in LuxU are demarcated using different colors, H1 (Asn7-Leu44, red), H2 (Gly46-Phe67, magenta), H3 (Ala69 to Leu88, yellow) and H4 (Glu97 to Ser111, blue). His58 in helix H2 is represented by a sphere
42485_2019_10_MOESM6_ESM.jpg (55 kb)
Supplementary material 6 (JPEG 54 kb) SM5. The motion captured by PC1 in LuxUQ with phosphorylated Asp107 (LuxQ in blue, and LuxU in green)
42485_2019_10_MOESM7_ESM.jpg (65 kb)
Supplementary material 7 (JPEG 64 kb) SM6. The motion captured by PC1 in LuxUQ with phosphorylated His58
42485_2019_10_MOESM8_ESM.mpg (5.1 mb)
Supplementary material 8 (MPG 5222 kb) SM7. Dynamics of unphosphorylated LuxUO. LuxU is shown in green and LuxO in orange cartoons, active site residues His58 in blue and Asp66 in red sticks
42485_2019_10_MOESM9_ESM.mpg (5.3 mb)
Supplementary material 9 (MPG 5435 kb) SM8. Dynamics of LuxUO with phosphorylated His58
42485_2019_10_MOESM10_ESM.mpg (4.2 mb)
Supplementary material 10 (MPG 4337 kb) SM9. Dynamics of LuxUO with phosphorylated Asp66
42485_2019_10_MOESM11_ESM.jpg (53 kb)
Supplementary material 11 (JPEG 53 kb) SM10. The motion captured by PC1 in unphosphorylated LuxUO. The protein backbone (Cα trace) is shown as ribbon (LuxU in green and LuxO in orange)
42485_2019_10_MOESM12_ESM.jpg (54 kb)
Supplementary material 12 (JPEG 53 kb) SM11. The motion captured by PC1 in LuxUO with phosphorylated His58
42485_2019_10_MOESM13_ESM.jpg (57 kb)
Supplementary material 13 (JPEG 57 kb) SM12. The motion captured by PC1 in LuxUO with phosphorylated Asp66


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of BiochemistryBose InstituteKolkataIndia
  2. 2.Bioinformatics CentreBose InstituteKolkataIndia
  3. 3.Indian Institute of Science Education and Research Tirupati (IISER-Tirupati)TirupatiIndia
  4. 4.Centre for Computational Biology, The University of KansasLawrenceUSA

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