2009 Nobel Prize in Chemistry
Reason for Award
for studies of the structure and function of the ribosome
Laureates
United States of America, 
India, 
United Kingdom of Great Britain and Northern Ireland
United States of America
Israel
Explanation
Proteins are the tiny building blocks that make up our bodies. The ribosome is the cell’s factory that makes these blocks. The laureates found out exactly what this factory looks like and how it works. They managed to take “pictures” of the ribosome at the level of individual atoms and saw how it puts proteins together one by one. Thanks to their work, scientists now have clues for making new medicines to fight disease.
Related Keywords
ribosome
The ribosome is a huge ribonucleoprotein complex that carries out protein synthesis and is classified as 70S in bacteria and 80S in eukaryotes. Structurally it is divided into a small and a large subunit that handle mRNA decoding and peptide-bond formation, respectively. Roughly two-thirds of its mass is ribosomal RNA and the remainder consists of several dozen ribosomal proteins. High-resolution structures published in 2000 revealed that the ribosome is itself a catalytic ribozyme. Many antibiotics target bacterial ribosomes, exploiting subtle differences from the human ribosome to act selectively. These features make the ribosome a central subject in evolutionary biology and drug discovery.
X-ray crystallography
X-ray crystallography is a cornerstone technique in structural biology that determines three-dimensional structures of proteins and nucleic acids at atomic resolution. A crystal, in which molecules are arranged in an ordered lattice, is exposed to X-rays, and the resulting diffraction pattern is analyzed to create an electron-density map. Phase information is recovered by methods such as multi-wavelength anomalous dispersion or heavy-atom soaking. For very large assemblies like the ribosome, cryogenic data collection and mitigation of radiation damage were essential. Technical breakthroughs around 2000 yielded data better than 3-Å resolution, propelling ribosome research forward. The method remains fundamental to mechanism studies and structure-based drug design.
rRNA
Ribosomal RNA (rRNA) constitutes the bulk of the ribosome’s mass and provides both its structural scaffold and its catalytic activity. The 16S rRNA in the small subunit forms the decoding center that verifies accurate base pairing between mRNA and tRNA. The 23S rRNA in the large subunit builds the peptidyl-transferase center that catalyzes peptide-bond formation between amino acids. Its higher-order structure comprises intertwined helices, loops and stems stabilized by Mg2+ ions. Because of its high conservation, rRNA also serves as a molecular chronometer for phylogenetic studies, offering clues to the history of evolution.
translation (protein synthesis)
Translation is the central biological process that converts the nucleotide sequence of mRNA into the amino-acid sequence of proteins. It proceeds through initiation, elongation and termination, each regulated by dedicated factors (IFs, EFs, RFs) that use the energy of GTP hydrolysis. The ribosome reads the mRNA three bases at a time, and the corresponding tRNA delivers the appropriate amino acid to be joined to the growing polypeptide chain. Multiple ribosomes can simultaneously run on a single mRNA, forming a polysome and boosting production efficiency. The error rate is as low as 10^-5, reflecting stringent quality-control mechanisms within the translational machinery.
peptide bond
The peptide bond is the covalent link that joins amino acids together to form the backbone of proteins. It is formed in the ribosomal peptidyl-transferase center (PTC) when the α-amino group of an aminoacyl-tRNA attacks the ester linkage of peptidyl-tRNA in a nucleophilic reaction. The PTC is composed entirely of rRNA; ribosomal proteins do not participate directly in catalysis. Hydrogen-bond networks and Mg2+ ions align substrates and neutralize charges, allowing the reaction to proceed at roughly 20 cycles per second. Antibiotics such as chloramphenicol block peptide-bond formation, halting bacterial protein synthesis and causing cell death.
antibiotic
Antibiotics are compounds that inhibit or kill bacteria, and many act by targeting the ribosome. Macrolides, aminoglycosides and tetracyclines, for example, bind to distinct ribosomal sites and disrupt different stages of translation. Aminoglycosides distort the decoding center and induce mistranslation, whereas macrolides plug the exit tunnel and arrest polypeptide elongation. The rise of resistant strains involves mutations in drug-binding sites and efflux pumps that expel antibiotics. Atomic ribosome structures supply the crucial information needed for rational design of new antibiotics capable of circumventing resistance.
tRNA
Transfer RNA (tRNA) is an adaptor molecule that matches mRNA codons with their corresponding amino acids; it is about 76 nucleotides long and folds into a cloverleaf secondary structure. An amino acid is attached via an ester bond to the 3′ end, while the anticodon loop base-pairs with mRNA inside the ribosome. During translation, tRNA moves sequentially through the A, P and E sites, delivering its amino acid and then exiting. Aminoacyl-tRNA synthetases ensure accuracy by ligating the correct amino acid to each tRNA. Some viruses and toxins mimic tRNA structures to hijack or disrupt host translation.
ribozyme
A ribozyme is an RNA molecule that possesses catalytic activity, exemplified by the peptidyl-transferase center of the ribosome. The existence of ribozymes supports the RNA-world hypothesis, which posits that early life used RNA both as genetic material and as a catalyst. Catalysis is aided by metal ions and intricate folding that position reactive groups, and some ribozymes approach protein enzymes in specificity and rate. Scientists have evolved artificial ribozymes for gene manipulation and molecular diagnostics. Discovering that the ribosome’s active site is a ribozyme revolutionized our understanding of protein-synthesis chemistry.