Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome.
Publication Type:Journal Article
Source:Science, Volume 335, Issue 6074, p.1370-2 (2012)
Keywords:Amino Acid Sequence, Carboxylic Ester Hydrolases, Crystallography, X-Ray, Escherichia coli, Escherichia coli Proteins, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Protein Biosynthesis, Protein Structure, Tertiary, Ribosome Subunits, Large, Bacterial, Ribosome Subunits, Small, Bacterial, Ribosomes, RNA, Bacterial, RNA, Messenger, RNA, Ribosomal, RNA, Transfer, Amino Acyl, RNA, Transfer, Met, Thermus thermophilus
<p>In bacteria, the hybrid transfer-messenger RNA (tmRNA) rescues ribosomes stalled on defective messenger RNAs (mRNAs). However, certain gram-negative bacteria have evolved proteins that are capable of rescuing stalled ribosomes in a tmRNA-independent manner. Here, we report a 3.2 angstrom-resolution crystal structure of the rescue factor YaeJ bound to the Thermus thermophilus 70S ribosome in complex with the initiator tRNA(i)(fMet) and a short mRNA. The structure reveals that the C-terminal tail of YaeJ functions as a sensor to discriminate between stalled and actively translating ribosomes by binding in the mRNA entry channel downstream of the A site between the head and shoulder of the 30S subunit. This allows the N-terminal globular domain to sample different conformations, so that its conserved GGQ motif is optimally positioned to catalyze the hydrolysis of peptidyl-tRNA. This structure gives insights into the mechanism of YaeJ function and provides a basis for understanding how it rescues stalled ribosomes.</p>