Differential processing of quorum sensing signals through phosphotransfer: structural insights from molecular dynamics simulations
- 6 Downloads
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.
KeywordsVibrio harveyi Quorum sensing Auto-inducer Signalling pathway proteins Molecular dynamics simulation
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.
- Faloon P, Weiner WS, Matharu DS, Neuenswander B, Porubsky P, Youngsaye W, Bennion M, Ng WL, Hurley A, Mosher CM, Johnston S, Dandapani S, Schoenen FJ, Aubé J, Munoz B, Palmer M, Bassler BL, Schreiber SL (2010–2013a) Probe reports from the NIH Molecular Libraries Program. National Center for Biotechnology Information (US), Bethesda (discovery of ML370, an inhibitor of Vibrio cholerae quorum sensing acting via the LuxO response regulator) Google Scholar
- Faloon P, Jewett I, Youngsaye W, Bennion M, Ng WL, Hurley A, Lewis, TA, Edwankar RV, Le H, Mosher CM, Johnston S, Dandapani S, Munoz B, Palmer M, Bassler BL, Schreiber SL (2010–2013b) Probe reports from the NIH Molecular Libraries Program. National Center for Biotechnology Information (US), Bethesda (discovery of ML366, an inhibitor of Vibrio cholerae quorum sensing acting via the LuxO response regulator) Google Scholar
- Patskovsky Y, Ramagopal UA, Fong R, Freeman J, Iizuka M, Groshong C, Smith D, Wasserman SR, Sauder JM, Burley SK, Almo SC (2008) (to be published) Google Scholar
- The PyMOL Molecular Graphics System, Version 1.8 (2019) Schrödinger, LLCGoogle Scholar
- Tu KC, Waters CM, Svenningsen SL, Bassler BL (2008) A small RNA-mediated negative feedback loop controls quorum-sensing dynamics in Vibrio harveyi. Mol Microbiol 70(4):896–907Google Scholar