title: Activators of the glutamate-dependent acid resistance system alleviate deleterious effects of YidC depletion in Escherichia coli.
abstract: The function of the essential inner membrane protein (IMP) YidC in Escherichia coli has been studied for a limited number of model IMPs and primarily using targeted approaches. These studies suggested that YidC acts at the level of insertion, folding, and quality control of IMPs, both in the context of the Sec translocon and as a separate entity. To further our understanding of YidC's role in IMP biogenesis, we screened a random overexpression library for factors that rescued the growth of cells upon YidC depletion. We found that the overexpression of the GadX and GadY regulators of the glutamate-dependent acid resistance system complemented the growth defect of YidC-depleted cells. Evidence is presented that GadXY overexpression counteracts the deleterious effects of YidC depletion on at least two fronts. First, GadXY prepares the cells for the decrease in respiratory capacity upon the depletion of YidC. Most likely, GadXY-regulated processes reduce the drop in proton-motive force that impairs the fitness of YidC-depleted cells. Second, in GadXY-overproducing cells increased levels of the general chaperone GroEL cofractionate with the inner membranes, which may help to keep newly synthesized inner membrane proteins in an insertion-competent state when YidC levels are limiting.
authors.affiliation: Department of Molecular Microbiology, Institute of Molecular Cell Biology, VU University Amsterdam, Amsterdam 1081 HV, The Netherlands.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yu
authors.forename: Martijn
authors.initials: M
authors.lastname: Bekker
authors.forename: Angela
authors.initials: A
authors.lastname: Tramonti
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cook
authors.forename: Peter
authors.initials: P
authors.lastname: van Ulsen
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Scheffers
authors.forename: Joost Teixeira
authors.initials: JT
authors.lastname: de Mattos
authors.forename: Daniela
authors.initials: D
authors.lastname: De Biase
authors.forename: Joen
authors.initials: J
authors.lastname: Luirink
mesh_terms: D051777:AraC Transcription Factor / Q000096:biosynthesis*; D018834:Chaperonin 60 / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D015870:Gene Expression; D005816:Genetic Complementation Test; D026901:Membrane Transport Proteins / Q000378:metabolism*; D050296:Microbial Viability; D058727:RNA, Small Untranslated / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D051777:AraC Transcription Factor; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; C446316:GadX protein, E coli; D026901:Membrane Transport Proteins; D058727:RNA, Small Untranslated; D014157:Transcription Factors; C412443:YIDC protein, E coli