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Description
Mitochondrion is a cellular organelle responsible for several crucial biochemical pathways. One of the most important is the respiratory chain followed by oxidative phosphorylation (OxPHOS), which is essential to produce cellular energy in the form of ATP. The reactions of the respiratory chain are carried out by respiratory chain complexes (RCCs). The genetic information for the synthesis of several essential RCC subunits is encoded in the mitochondrial genome (mtDNA). Mitochondrial ribosomes (mitoribosomes) are biomacromolecular complexes located within mitochondria. Mitoribosomes are responsible for performing the final step of mtDNA expression - mitochondrial translation which takes place isolated from the cytosolic translation. Proper mitoribosomal function directly affects one of the central processes of cellular metabolism. Therefore, a detailed understanding of mitoribosomal behaviour is of great importance with potential applications in cancer therapy and longevity.
Here we present a full all-atom simulation model of the human mitoribosome in explicit solvent. To the best of our knowledge, this is the first [K(2.1][RK2.2]simulation model of a mitoribosome completed under such conditions. We use the simulation model to describe the dynamics of the selected mitoribosomal parts. We focus on comparison of the human mitoribosome with a bacterial ribosome, as these two ribosomes share a lot of structural similarities and evolutionary origin.
The simulation model was validated against the available cryo-EM model using basic analytical metrics RMSD, RMSF, and radius of gyration. According to RMSD and RMSF values we have revealed the most static and the most flexible regions of the mitoribosome.
Overall, our model opens a way for studies of mitochondrial ribosome dynamics at atomic detail.