PMID:22422986

Citation	Gagnon, MG, Seetharaman, SV, Bulkley, D and Steitz, TA (2012) Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science 335:1370-2
Abstract	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.
Links	PubMed PMC3377438 Online version:10.1126/science.1217443
Keywords	Amino Acid Sequence; Carboxylic Ester Hydrolases/chemistry; Carboxylic Ester Hydrolases/metabolism; Crystallography, X-Ray; Escherichia coli/chemistry; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Protein Biosynthesis; Protein Structure, Tertiary; RNA, Bacterial/chemistry; RNA, Bacterial/metabolism; RNA, Messenger/chemistry; RNA, Messenger/metabolism; RNA, Ribosomal/chemistry; RNA, Ribosomal/metabolism; RNA, Transfer, Amino Acyl/chemistry; RNA, Transfer, Amino Acyl/metabolism; RNA, Transfer, Met/chemistry; RNA, Transfer, Met/metabolism; Ribosome Subunits, Large, Bacterial/chemistry; Ribosome Subunits, Large, Bacterial/metabolism; Ribosome Subunits, Small, Bacterial/chemistry; Ribosome Subunits, Small, Bacterial/metabolism; Ribosomes/chemistry; Ribosomes/metabolism; Thermus thermophilus/chemistry; Thermus thermophilus/metabolism; Thermus thermophilus/ultrastructure
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