Polar bears, antibiotics, and the evolving ribosome (Nobel Lecture).
High-resolution structures of ribosomes, the cellular machines that translate the genetic code into proteins, revealed the decoding mechanism, detected the mRNA path, identified the sites of the tRNA molecules in the ribosome, elucidated the position and the nature of the nascent proteins exit tunnel, illuminated the interactions of the ribosome with non-ribosomal factors, such as the initiation, release and recycling factors, and provided valuable information on ribosomal antibiotics, their binding sites, modes of action, principles of selectivity and the mechanisms leading to their resistance. Notably, these structures proved that the ribosome is a ribozyme whose active site, namely where the peptide bonds are being formed, is situated within a universal symmetrical region that is embedded in the otherwise asymmetric ribosome structure. As this symmetrical region is highly conserved and provides the machinery required for peptide bond formation and for ribosome polymerase activity, it may be the remnant of the proto-ribosome, a dimeric prebiotic machine that formed peptide bonds and non-coded polypeptide chains. Structures of complexes of ribosomes with antibiotics targeting them revealed the principles allowing for their clinical use, identified resistance mechanisms and showed the structural bases for discriminating pathogenic bacteria from hosts, hence providing valuable structural information for antibiotics improvement and for the design of novel compounds that can serve as antibiotics.
Yonath
Ada
A
Department of Structural Biology, Weizmann Institute, 76100 Rehovot, Israel. ada.yonath@weizmann.ac.il
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001671:Biochemistry / Q000266:history*; D018360:Crystallography, X-Ray; D049674:History, 21st Century; D007557:Israel; D009613:Nobel Prize; D017434:Protein Structure, Tertiary; D012343:RNA, Transfer / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*; D001503:Ursidae
D000900:Anti-Bacterial Agents; D012343:RNA, Transfer