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Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation.

<div class='caption-title'>Cryo-EM structures of the 70 S ribosome initiation complex bound to IF2-GDP and IF2-GDPCP.</div>
<div class='caption-title'>Nucleotide-binding pocket in the G-domain of IF2.</div>
<div class='caption-title'>Structural rearrangements in IF2.</div>
Basu RS, Sherman MB, Gagnon MG
OpenAccess logo Nat Commun 13 3388 (2022)
Cited: 4 times
EuropePMC logo PMID: 35697706

Abstract

During translation initiation, initiation factor 2 (IF2) holds initiator transfer RNA (fMet-tRNAifMet) in a specific orientation in the peptidyl (P) site of the ribosome. Upon subunit joining IF2 hydrolyzes GTP and, concomitant with inorganic phosphate (Pi) release, changes conformation facilitating fMet-tRNAifMet accommodation into the P site and transition of the 70 S ribosome initiation complex (70S-IC) to an elongation-competent ribosome. The mechanism by which IF2 separates from initiator tRNA at the end of translation initiation remains elusive. Here, we report cryo-electron microscopy (cryo-EM) structures of the 70S-IC from Pseudomonas aeruginosa bound to compact IF2-GDP and initiator tRNA. Relative to GTP-bound IF2, rotation of the switch 2 α-helix in the G-domain bound to GDP unlocks a cascade of large-domain movements in IF2 that propagate to the distal tRNA-binding domain C2. The C2-domain relocates 35 angstroms away from tRNA, explaining how IF2 makes way for fMet-tRNAifMet accommodation into the P site. Our findings provide the basis by which IF2 gates the ribosome to the elongation phase.

Articles citing this publication (4)

  1. Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin. Paranjpe MN, Marina VI, Grachev AA, Maviza TP, Tolicheva OA, Paleskava A, Osterman IA, Sergiev PV, Konevega AL, Polikanov YS, Gagnon MG. Nucleic Acids Res 51 449-462 (2023)
  2. Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria. Parajuli NP, Emmerich A, Mandava CS, Pavlov MY, Sanyal S. Nat Commun 14 918 (2023)
  3. Interactions between terminal ribosomal RNA helices stabilize the E. coli large ribosomal subunit. Nissley AJ, Kamal TS, Cate JHD. RNA 29 1500-1508 (2023)
  4. Salt-Specific Suppression of the Cold Denaturation of Thermophilic Multidomain Initiation Factor 2. Džupponová V, Tomášková N, Antošová A, Sedlák E, Žoldák G. Int J Mol Sci 24 6787 (2023)


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