title: A single amino acid of a Salmonella virulence protein contributes to pathogenicity by protecting from the FtsH-mediated proteolysis.
abstract: FtsH is a membrane-bound ATP-dependent protease in bacteria that is critical for degrading membrane proteins. The MgtC virulence protein from Salmonella enterica is located at the inner membrane and required for survival inside macrophages. Here we report that a single substitution at tryptophan 226 of the MgtC protein to alanine promotes the FtsH-mediated proteolysis. The Trp residue is located at the very C-terminus of the cytoplasmic domain of the MgtC protein and conserved only in intracellular pathogens surviving within a macrophage phagosome, suggesting that Salmonella may acquire the tryptophan residue to prevent MgtC degradation by the FtsH protease. Moreover, the reduced proteolytic activity of the FtsH protease during infection further increases MgtC production, promoting Salmonella's pathogenicity inside phagocytic cells.
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Eunna
authors.initials: E
authors.lastname: Choi
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Kyoung
authors.initials: K
authors.lastname: Kwon
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea. Electronic address: eunjinlee@khu.ac.kr.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D049069:ATP-Dependent Proteases / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability; D008954:Models, Biological; D009154:Mutation; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D059748:Proteolysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019779:Salmonella enterica / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D013379:Substrate Specificity; D014364:Tryptophan / Q000737:chemistry*; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D014364:Tryptophan; D049069:ATP-Dependent Proteases
keywords: FtsH protease; Posttranslational regulation; mgtC