Decoding life: the underside of ribosome
The ribosome translates the genetic code into protein, but the structural basis for the high accuracy was still a puzzle. X-ray crystal structures of ribosomal complexes provide a new understanding of discrimination between correct and non-correct transfer RNAs.
Nature March 21, 2012
March 21, 2012
Specialized on the ribosome, a complex cellular structure responsible for the protein synthesis, Marat Yusupov team has just published their results about the mechanisms of one of the stages of protein synthesis, the decoding. The decoding of the genetic information on the ribosome is a universal process, which exists in all living cells from bacteria to higher eukaryotes, and enables the ribosome to ensure this process reliability. These data published on March 21st 2012 in Nature are bringing to light a physical phenomenon that allows the ribosome to select with accuracy amino acids corresponding with the genetic information. They are bringing other vision of decoding mechanism on the ribosome than it was published one decade ago and which is a reference.
Decoding, a main stage of protein synthesis
Synthesis of proteins sets in two main stages. The first one enables the cell to transcript genetic information from DNA to messenger RNA (mRNA). In a second step, these mRNAs are translated into proteins within complex cellular structures, the ribosomes. These structures “read” mRNA triplets and select appropriate transfer RNA (tRNA). These tRNA are carrying amino acids that form a protein when linked together. Ribosomes are able to “choose” correct tRNAs that match mRNAs. This decoding mechanism runs particularly smoothly since only one mistake occurs among the thousands of tRNA that are recruited on the ribosome!
A totally new recognition mechanism
In parallel with their work on crystal structure determination of the full 80S eukaryotic ribosome, Marat Yusupov team also studies the mechanism of protein biosynthesis on ribosome using X-Ray analysis. “The main question was to understand how the ribosome is able to select precisely the correct transfer RNA among all those that are in the cell” explains Gulnara Yusupova, responsible for the project. To solve this question, researchers have relied on structural data that brought to light a very particular mechanism in the decoding site. All tRNA can reach this site on the ribosome. When a tRNA matches the mRNA codon that has to be translated, the translation process occurs and the amino acid is added to the protein being translated. On the other hand, when the tRNA entering the site differs little, the “mold” of the decoding site forces the matching of the bad tRNA with mRNA and its shape widens. This distortion and the energy requested that would cause the rejection of the wrong tRNA. This mechanism allows the ribosome to “sort out” cognate from near-cognate tRNA and is the main guarantee of protein synthesis.
These results are challenging decoding mechanisms proposed in 2000 by Venkatraman Ramakrishnan, Nobel prize in chemistry (2009). Indeed “At that time researchers have just worked on a part of the ribosome, on the contrary to our study that considers its whole structure” Gulnara Yusupova added. These results also question the current knowledge of action mechanisms of an antibiotic: the paromomycin. Though molecular models of combining mechanisms of this antibiotic with ribosome are currently used for drug design.
Besides, let us note that Marat Yusupov and Gulnara Yusupova have just been awarded with the Gregori Aminoff prize from the Royal Swedish Academy of Science, a very prestigious prize in the field of crystallography.