Abstract
A tightly controlled turnover of membrane proteins is required for lipid bilayer stability, cell metabolism, and cell viability. Among the energy-dependent AAA+ proteases in Salmonella, FtsH is the only membrane-bound protease that contributes to the quality control of membrane proteins. FtsH preferentially degrades the C-terminus or N-terminus of misfolded, misassembled, or damaged proteins to maintain physiological functions. We found that FtsH hydrolyzes the Salmonella MgtC virulence protein when we substitute the MgtC 226th Trp, which is well conserved in other intracellular pathogens and normally protects MgtC from the FtsH-mediated proteolysis. Here we investigate a rule determining the FtsH-mediated proteolysis of the MgtC protein at Trp226 residue. Substitution of MgtC tryptophan 226th residue to alanine, glycine, or tyrosine leads to MgtC proteolysis in a manner dependent on the FtsH protease whereas substitution to phenylalanine, methionine, isoleucine, leucine, or valine resists MgtC degradation by FtsH. These data indicate that a large and hydrophobic side chain at 226th residue is required for protection from the FtsH-mediated MgtC proteolysis.
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Alix, E. and Blanc-Potard, A.B. 2007. MgtC: A key player in intramacrophage survival. Trends Microbiol. 15, 252–256.
Alix, E. and Blanc-Potard, A.B. 2008. Peptide-assisted degradation of the Salmonella MgtC virulence factor. EMBO J. 27, 546–557.
Bader, M.W., Sanowar, S., Daley, M.E., Schneider, A.R., Cho, U., Xu, W., Klevit, R.E., Le Moual, H., and Miller, S.I. 2005. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122, 461–472.
Blanc-Potard, A.B. and Groisman, E.A. 1997. The Salmonella selC locus contains a pathogenicity island mediating intramacrophage survival. EMBO J. 16, 5376–5385.
Blanc-Potard, A.B. and Lafay, B. 2003. MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: Evidence from molecular phylogeny and comparative genomics. J. Mol. Evol. 57, 479–486.
Buchmeier, N., Blanc-Potard, A., Ehrt, S., Piddington, D., Riley, L., and Groisman, E.A. 2000. A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica. Mol. Microbiol. 35, 1375–1382.
Chiba, S., Akiyama, Y., and Ito, K. 2002. Membrane protein degradation by FtsH can be initiated from either end. J. Bacteriol. 184, 4775–4782.
Choi, E., Kwon, K., and Lee, E.J. 2015. A single amino acid of a Salmonella virulence protein contributes to pathogenicity by protecting from the FtsH-mediated proteolysis. FEBS Lett. 589, 1346–1351.
Davis, R.W., Bolstein, D., and Roth, J.R. 1980. Advanced bacterial genetics. Cold Spring Harbor Lab.
Fields, P.I., Swanson, R.V., Haidaris, C.G., and Heffron, F. 1986. Mutants of Salmonella Typhimurium that cannot survive within the macrophage are avirulent. Proc. Natl. Acad. Sci. USA 83, 5189–5193.
Garcia Vescovi, E., Soncini, F.C., and Groisman, E.A. 1996. Mg2+ as an extracellular signal: Environmental regulation of Salmonella virulence. Cell 84, 165–174.
Grabenstein, J.P., Fukuto, H.S., Palmer, L.E., and Bliska, J.B. 2006. Characterization of phagosome trafficking and identification of PhoP-regulated genes important for survival of Yersinia pestis in macrophages. Infect. Immun. 74, 3727–3741.
Ito, K. and Akiyama, Y. 2005. Cellular functions, mechanism of action, and regulation of FtsH protease. Annu. Rev. Microbiol. 59, 211–231.
Kim, H., Lee, H., and Shin, D. 2013. The FeoC protein leads to high cellular levels of the Fe(II) transporter FeoB by preventing FtsH protease regulation of FeoB in Salmonella enterica. J. Bacteriol. 195, 3364–3370.
Langklotz, S., Baumann, U., and Narberhaus, F. 2012. Structure and function of the bacterial AAA protease FtsH. Biochim. Biophys. Acta 1823, 40–48.
Lavigne, J.P., O’Callaghan, D., and Blanc-Potard, A.B. 2005. Requirement of MgtC for Brucella suis intramacrophage growth: A potential mechanism shared by Salmonella enterica and Mycobacterium tuberculosis for adaptation to a low-Mg2+ environment. Infect. Immun. 73, 3160–3163.
Lee, E.J., Choi, J., and Groisman, E.A. 2014. Control of a Salmonella virulence operon by proline-charged tRNApro. Proc. Natl. Acad. Sci. USA 111, 3140–3145.
Lee, E.J. and Groisman, E.A. 2010. An antisense RNA that governs the expression kinetics of a multifunctional virulence gene. Mol. Microbiol. 76, 1020–1033.
Lee, E.J. and Groisman, E.A. 2012a. Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. Nature 486, 271–275.
Lee, E.J. and Groisman, E.A. 2012b. Tandem attenuators control expression of the Salmonella mgtCBR virulence operon. Mol. Microbiol. 86, 212–224.
Lee, E.J., Pontes, M.H., and Groisman, E.A. 2013. A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium’s own F1Fo ATP synthase. Cell 154, 146–156.
Maloney, K.E. and Valvano, M.A. 2006. The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium limitation conditions and intracellular survival in macrophages. Infect. Immun. 74, 5477–5486.
Maloy, S.R. and Nunn, W.D. 1981. Selection for loss of tetracycline resistance by Escherichia coli. J. Bacteriol. 145, 1110–1111.
Nam, D., Choi, E., Shin, D., and Lee, E.J. 2016. tRNApro-mediated downregulation of elongation factor P is required for mgtCBR expression during Salmonella infection. Mol. Microbiol. 102, 221–232.
Pontes, M.H., Lee, E.J., Choi, J., and Groisman, E.A. 2015. Salmonella promotes virulence by repressing cellulose production. Proc. Natl. Acad. Sci. USA 112, 5183–5188.
Prost, L.R., Daley, M.E., Le Sage, V., Bader, M.W., Le Moual, H., Klevit, R.E., and Miller, S.I. 2007. Activation of the bacterial sensor kinase PhoQ by acidic pH. Mol. Cell. 26, 165–174.
Rang, C., Alix, E., Felix, C., Heitz, A., Tasse, L., and Blanc-Potard, A.B. 2007. Dual role of the MgtC virulence factor in host and non-host environments. Mol. Microbiol. 63, 605–622.
Snavely, M.D., Miller, C.G., and Maguire, M.E. 1991. The mgtB Mg2+ transport locus of Salmonella typhimurium encodes a P-type ATPase. J. Biol. Chem. 266, 815–823.
Soncini, F.C., Garcia Vescovi, E., Solomon, F., and Groisman, E.A. 1996. Molecular basis of the magnesium deprivation response in Salmonella typhimurium: Identification of PhoP-regulated genes. J. Bacteriol. 178, 5092–5099.
Tomoyasu, T., Yamanaka, K., Murata, K., Suzaki, T., Bouloc, P., Kato, A., Niki, H., Hiraga, S., and Ogura, T. 1993. Topology and subcellular localization of FtsH protein in Escherichia coli. J. Bacteriol. 175, 1352–1357.
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Baek, J., Choi, E. & Lee, EJ. A rule governing the FtsH-mediated proteolysis of the MgtC virulence protein from Salmonella enterica serovar Typhimurium. J Microbiol. 56, 565–570 (2018). https://doi.org/10.1007/s12275-018-8245-6
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DOI: https://doi.org/10.1007/s12275-018-8245-6