Dynamical networks in tRNA:protein complexes

Abstract

Community network analysis derived from molecular dynamics simulations is used to identify and compare the signaling pathways in a bacterial glutamyl-tRNA synthetase (GluRS):tRNA(Glu) and an archaeal leucyl-tRNA synthetase (LeuRS):tRNA(Leu) complex. Although the 2 class I synthetases have remarkably different interactions with their cognate tRNAs, the allosteric networks for charging tRNA with the correct amino acid display considerable similarities. A dynamic contact map defines the edges connecting nodes (amino acids and nucleotides) in the physical network whose overall topology is presented as a network of communities, local substructures that are highly intraconnected, but loosely interconnected. Whereas nodes within a single community can communicate through many alternate pathways, the communication between monomers in different communities has to take place through a smaller number of critical edges or interactions. Consistent with this analysis, there are a large number of suboptimal paths that can be used for communication between the identity elements on the tRNAs and the catalytic site in the aaRS:tRNA complexes. Residues and nucleotides in the majority of pathways for intercommunity signal transmission are evolutionarily conserved and are predicted to be important for allosteric signaling. The same monomers are also found in a majority of the suboptimal paths. Modifying these residues or nucleotides has a large effect on the communication pathways in the protein:RNA complex consistent with kinetic data.

Fig. 1.

Correlation analysis (C_ij) of the motion during a 20-ns MD simulation of the GluRS complex. Monomers with highly (anti)correlated motion are orange or red (blue). Distant (>15Å) regions displaying high degree of (anti)correlation are marked in white rectangles (below)above the diagonal.

Fig. 2.

Difference in characteristic path length: the change in CPL upon edge removal for each nucleotide at the interface of tRNA^Glu in the GluRS network. The nucleotides with significant increase in CPL are labeled.

Fig. 3.

Community analysis of the network formed based on the GluRS adenylate simulation. (A and B) The monomers are colored (A) according to community membership calculated in B: cyan, 1; purple, 2; orange, 3; green, 4; lime, 5; blue, 6; tan, 7; black, 8; yellow, 9; red, 10; and ochre, 11. Hard spheres indicate residues that occur in a majority of shortest paths connecting nodes in different communities. The width of the lines is proportional to the betweenness of the edge (number of shortest paths passing through that edge). (C) Community network representation: The width of the lines is proportional to the number of shortest paths passing through those junctions, and the presence of an identity element in a community is indicated by an asterisk. (D) Community network for modified system in which all contacts between U13 and GluRS are weakened. The isolated communities made of the single nucleotides (U20A and U59) are not shown in the community networks.

Fig. 4.

Scaled community network of the LeuRS:tRNA adenylate complex.