Computational simulations study of Helixes 90-92

I. Beššeová, K. Réblová, J. Šponer

Institute of Biophysics, ASCR, v.v.i., Královopolská 135, 612 65 Brno

The Helix 90-92 system is a monomeric part of a 50S large ribosomal subunit from domain V of 23S rRNA. It is classified as a 3-way junction family, type C. Helix 92 represents crucial component of ribosomal peptidyltransferase center. Its most important part is a hairpin loop known as A-loop. A-loop directly interacts with aminoacyl-tRNA within the protein synthesis. These interactions, orienting tRNA properly and correctly to ribosome, involve Watson–Crick interactions between rRNA and universally conserved nucleotides 3´-end tRNA (C75). Kinetically slowest step by the selection of tRNA is the accommodation of aatRNA to A-site, followed by the release of Tu-factor from aatRNA and subsequently resulting to the rise of rapid peptide bond. This accommodation step includes the recognition of aatRNA by A-loop and the movement of A-site tRNA to proper position in the active site. Unfortunately, the exact nature of rearrangements occurring during accommodation of tRNA into the peptidyltransferase center remains still unclear.

Nowadays, posttranscriptional modification of this rRNA system was observed and shows the metylation of U2552 (2’-O-methyl). Thus the Helix 90-92 simulations can be divided into two main groups: Systems without and with methyled residue.

The project is devoted to three major subjects:

1)to describe the methylation impact on Helix 92 conformation – mainly on U2552-C2556 base pair 2)to characterize the overall structural dynamics and motions of the whole system and 3)to input simulated structures of Helices 90-92 into the context with the ribosome.