Molecular dynamics investigation of a mechanism of allosteric signal transmission in ribosomes

Abstract

The ribosome is a molecular machine that synthesizes all cellular proteins via translation of genetic information encoded in polynucleotide chain of messenger RNA. Transition between different stages of the ribosome working cycle is strictly coordinated by changes in structure and mutual position both of subunits of the ribosome and its ligands. Therein, information regarding structural transformations is transmitted between functional centers of the ribosome through specific signals. Usually, functional centers of ribosomes are located at a distance reaching up to several tens of angstroms, and it is believed that such signals are transduced allosterically. In our study, we attempted to answer the question of how allosteric signal can be transmitted from one of the so-called sensory elements of ribosomal tunnel (RT) to the peptidyl transferase center (PTC). A segment of RT wall from the E. coli ribosome composed of nucleotide residues A2058, A2059, m(2)A2503, G2061, A2062, and C2063 of its 23S rRNA was examined by molecular dynamics simulations. It was found that a potential signal transduction pathway A2058-C2063 acted as a dynamic ensemble of interdependent conformational states, wherein cascade-like changes can occur. It was assumed that structural rearrangement in the A2058-C2063 RT segment results in reversible inactivation of PTC due to a strong stacking contact between functionally important U2585 residue of the PTC and nucleotide residue C2063. A potential role for the observed conformational transition in the A2058-C2063 segment for regulating ribosome activity is discussed.

Neuron-Like Networks Between Ribosomal Proteins Within the Ribosome

“…Viewing ribosomal protein extensions as connecting wires that play a role in information transfer is consistent with experimental data showing that RNA 21 22 and some proteins 23 24 25 participate in allosteric coordination and information exchange between distant parts of the ribosome. In addition, our study provides new structural insights to decipher the molecular mechanisms of allosteric communication within disordered proteins 26 27 .…”

Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain

“…Therefore A2062 seems to be perfectly located to sense the nascent polypeptide chain and communicate the stalling signal to the PTC. The crucial role of A2503 and A2062 for signal transmission was also emphasized by molecular dynamics simulations (41). A2062 is universally conserved and highly flexible (42).…”

Tracking fluctuation hotspots on the yeast ribosome through the elongation cycle

“…A recent computational analysis of conserved contacts between ribosomal protein extensions revealed protein-based circuits analogous to neural networks organized along the path of tRNA translocation, and around the peptide exit tunnel (78). Classical genetic studies, in which networks are identified by their disruption upon mutation of key interacting elements located both in ribosomal proteins and rRNAs, have been critical in identifying many of the rRNA-based allosteric information exchange networks revealed here (32,33,53–55,57,67,70,71,79–82). …”