How Hibernation Factors RMF, HPF, and YfiA Turn Off Protein Synthesis

• Published in: Science (American Association for the Advancement of Science) 2012-05, Vol.336 (6083), p.915-918
• Main Authors: Polikanov, Yury S., Blaha, Gregor M., Steitz, Thomas A.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Analytical, structural and metabolic biochemistry; Bacteria; Bacterial proteins; Bacterial Proteins - biosynthesis; BASIC BIOLOGICAL SCIENCES; Binding; Binding Sites; Biological and medical sciences; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; Crystalline structure; Crystallography, X-Ray; DIMERS; E coli; Electron density; ESCHERICHIA COLI; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; HIBERNATION; MESSENGER-RNA; Microbiology; Models, Molecular; MODULATION; Molecular biophysics; MONOMERS; Peptide Chain Initiation, Translational; Prokaryotic Initiation Factors - metabolism; Promotion; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Protein synthesis; PROTEINS; Ribonucleic acid; Ribonucleic acids; Ribosomal proteins; Ribosomal Proteins - chemistry; Ribosomal Proteins - metabolism; RIBOSOMAL RNA; Ribosome Subunits, Small, Bacterial - chemistry; Ribosome Subunits, Small, Bacterial - metabolism; Ribosome Subunits, Small, Bacterial - ultrastructure; RIBOSOMES; Ribosomes - chemistry; Ribosomes - metabolism; Ribosomes - ultrastructure; RNA; RNA, Bacterial - chemistry; RNA, Bacterial - metabolism; RNA, Messenger - chemistry; RNA, Messenger - metabolism; RNA, Ribosomal, 16S - chemistry; RNA, Ribosomal, 16S - metabolism; RNA, Transfer - chemistry; RNA, Transfer - metabolism; Structure in molecular biology; SYNTHESIS; Thermus thermophilus - chemistry; TRANSFER RNA; Translations
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1218538

Eubacteria inactivate their ribosomes as 100S dimers or 705 monomers upon entry into stationary phase. In Eschenchia coli, 1005 dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 705 monomers. Here, we present high-resolution crystal structures of the Thermus thermophilus 70S ribosome in complex with each of these stationary-phase factors. The binding site of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence, which prevents the interaction between the mRNA and the 165 ribosomal RNA. The nearly identical binding sites of HPF and YfiA overlap with those of the mRNA, transfer RNA, and initiation factors, which prevents translation initiation. The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation.