VapC20 of Mycobacterium tuberculosis Cleaves the Sarcin Ricin Loop of 23S rRNA

Publikation: Forskning - peer reviewTidsskriftartikel

Dokumenter

DOI

  • Kristoffer Skovbo Winther
    Kristoffer Skovbo WintherNewcastle UniversityStorbritannien
  • Ditlev E. Brodersen
  • Alistair K Brown
    Alistair K Brown Northumbria UniversityStorbritannien
  • Kenn Gerdes
    Kenn GerdesUniversity of NewcastleStorbritannien
The highly persistent and often lethal human pathogen, Mycobacterium tuberculosis contains at least 88 toxin–antitoxin genes. More than half of these encode VapC PIN domain endoribonucleases that inhibit cell growth by unknown mechanisms. Here we show that VapC20 of M. tuberculosis inhibits translation by cleavage of the Sarcin–Ricin loop (SRL) of 23S ribosomal RNA at the same position where Sarcin and other eukaryotic ribotoxins cleave. Toxin-inhibited cells can be rescued by the expression of the antitoxin, thereby raising the possibility that vapC20 contributes to the extreme persistence exhibited by M. tuberculosis. VapC20 cleavage is inhibited by mutations in the SRL that flank the cleavage site but not by changes elsewhere in the loop. Disruption of the SRL stem abolishes cleavage; however, further mutations that restore the SRL stem structure restore cleavage, revealing that the structure rather than the exact sequence of the SRL is important for this activity
OriginalsprogEngelsk
Artikelnummer2796
TidsskriftNature Communications
Vol/bind4
Antal sider9
ISSN2041-1723
DOI
StatusUdgivet - 14 nov. 2013

Se relationer på Aarhus Universitet Citationsformater

Download-statistik

Ingen data tilgængelig

ID: 56496822