Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide.

Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream open reading frame 2 (uORF2). The C terminus of the AAP appears to be compacted adjacent to the peptidyl transferase center (PTC). Both nascent chains interact with ribosomal proteins L4 and L17 at tunnel constriction in a distinct fashion. Significant changes at the PTC were observed: the eukaryotic-specific loop of ribosomal protein L10e establishes direct contact with the CCA end of the peptidyl-tRNA (P-tRNA), which may be critical for silencing of the PTC during translational stalling. Our findings provide direct structural insight into two distinct eukaryotic stalling processes. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Shashi Bhushan, Helge Meyer, Agata L Starosta, Thomas Becker, Thorsten Mielke, Otto Berninghausen, Michael Sattler, Daniel N Wilson, Roland Beckmann. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. Molecular cell. 2010 Oct 8;40(1):138-46

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PMID: 20932481

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