5IWA

Crystal structure of the 30S ribosomal subunit from Thermus thermophilus in complex with the GE81112 peptide antibiotic

Summary for 5IWA

• Entry DOI: 10.2210/pdb5iwa/pdb
• Descriptor: 30S ribosomal protein S2, 30S ribosomal protein S11, 30S ribosomal protein S12, ... (24 entities in total)
• Functional Keywords: protein synthesis, translation initiation, ribosome, antibiotic, translation
• Biological source: Thermus thermophilus HB8; More
• Total number of polymer chains: 21
• Total formula weight: 769656.87

Authors

Schedlbauer, A.,Kaminishi, T.,Ochoa-Lizarralde, B.,Chieko, N.,Masahito, K.,Takemoto, C.,Yokoyama, S.,Connell, S.R.,Fucini, P. (deposition date: 2016-03-22, release date: 2016-04-27, Last modification date: 2024-01-10)

Primary citation

Fabbretti, A.,Schedlbauer, A.,Brandi, L.,Kaminishi, T.,Giuliodori, A.M.,Garofalo, R.,Ochoa-Lizarralde, B.,Takemoto, C.,Yokoyama, S.,Connell, S.R.,Gualerzi, C.O.,Fucini, P.
Inhibition of translation initiation complex formation by GE81112 unravels a 16S rRNA structural switch involved in P-site decoding.
Proc.Natl.Acad.Sci.USA, 113:E2286-E2295, 2016

PubMed Abstract: In prokaryotic systems, the initiation phase of protein synthesis is governed by the presence of initiation factors that guide the transition of the small ribosomal subunit (30S) from an unlocked preinitiation complex (30S preIC) to a locked initiation complex (30SIC) upon the formation of a correct codon-anticodon interaction in the peptidyl (P) site. Biochemical and structural characterization of GE81112, a translational inhibitor specific for the initiation phase, indicates that the main mechanism of action of this antibiotic is to prevent P-site decoding by stabilizing the anticodon stem loop of the initiator tRNA in a distorted conformation. This distortion stalls initiation in the unlocked 30S preIC state characterized by tighter IF3 binding and a reduced association rate for the 50S subunit. At the structural level we observe that in the presence of GE81112 the h44/h45/h24a interface, which is part of the IF3 binding site and forms ribosomal intersubunit bridges, preferentially adopts a disengaged conformation. Accordingly, the findings reveal that the dynamic equilibrium between the disengaged and engaged conformations of the h44/h45/h24a interface regulates the progression of protein synthesis, acting as a molecular switch that senses and couples the 30S P-site decoding step of translation initiation to the transition from an unlocked preIC to a locked 30SIC state.

PubMed: 27071098
DOI: 10.1073/pnas.1521156113

Experimental method

X-RAY DIFFRACTION (3.5 Å)