Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Identification of the Evolving RNA Nano-machine for Protein Biosynthesis Within the Contemporary Ribosome
Ribosomes, the universal cellular nano-machines, act as polymerases that translate the genetic code into proteins with high efficiency. The ribosome?s active site, the peptidyl transferase center (PTC), resides within a highly conserved region of the contemporary large ribosomal subunit. Comprised of 180 nucleotides arranged as a pseudo symmetrical two-fold region in all known ribosome structures, this region confines a void that provides the space required for the production of the nascent proteins and contains all of the structural elements required for navigating the formation of nascent proteins.
The elaborate architecture of this region is capable of positioning both the amino acylated and peptidyl tRNA substrates in stereochemistry required for peptide bond formation, for substrate-mediated catalysis, and for substrate translocation. Hence, enabling the repetition of peptide bond formation and facilitating amino acid polymerization.
The overall fold of the RNA backbone of this region resembles motifs identified in ancient as well as in contemporary RNA molecules of comparable size. Consistently, the extremely high conservation of this region throughout all known kingdoms of life implies its existence beyond environmental conditions. The universality of the three dimensional structure of this region and its central location within the ribosome indicate that this region may represent the proto-ribosome and support the hypothesis that the proto-ribosome evolved by gene duplication or gene fusion. This could have been performed by the RNA since it can act as an enzyme and replicate its own template.
Although the proto-ribosome can act as a ribozyme, on its own it provides only a modest level of activity, mainly owing to its seemingly limited structural stability and rather loose substrate accommodation. A substantial increase in the catalytic rate could have been generated by peripheral RNA elements and proteins or peptides. Appearance of polypeptides that can perform required functions more efficient than ribozymes triggered the emergence of peptide bond formation associated by decoding of genetic information.
Experimental results and conceptual issues will be presented and discussed.
Department of Structural Biology