Scheme of enterovirus genome release. Binding to receptors or exposure to acidic pH in endosomes induces conformational transition of virions to activated particles. The structural changes within the capsid and virus RNA enable the expulsion of pentamers from the capsid, resulting in the formation of open particles. The RNA genomes are released from the open particles. After the genome release, the pentamers may re-associate with the open capsids. Scale bar represents 10 nm

Pavel Plevka Research Group

Significance

Viruses from the genus Enterovirusare important human pathogens. Receptor binding or exposure to acidic pH in endosomes converts enterovirus particles to an activated state that is required for genome release. However, the mechanism of enterovirus uncoating is not well understood. Here, we use cryo-electron microscopy to visualize virions of human echovirus 18 in the process of genome release. We discover that the exit of the RNA from the particle of echovirus 18 results in a loss of one, two, or three adjacent capsid-protein pentamers. The opening in the capsid, which is more than 120 Å in diameter, enables the release of the genome without the need to unwind its putative double-stranded RNA segments. We also detect capsids lacking pentamers during genome release from echovirus 30. Thus, our findings uncover a mechanism of enterovirus genome release that could become target for antiviral drugs

Buchta, D., Füzik, T., Hrebík, D., Levdansky, Y., Sukeník, L., Mukhamedova, L., Moravcová, J., Vácha, R., and Plevka, P: Enterovirus particles expel capsid pentamers to enable genome release, Nature Commun. (2019)10, 1138, 1-9  doi.org/10.1038/s41467-019-09132-x

(A) Model of TvTom40-2 was built using the N. crassa Tom40 structure (PDB ID 5o8o) as a template. The asterisk shows the extra loop between β-strands five and six, and the arrow shows the loop between β-strands four and five. (B) Comparison of 3D structures of N. crassa Tom40 (5o8o), TvTom40-2, and Mus musculus VDAC (3emn). Mouse VDAC is almost uniformly positively charged inside the barrel to bind negatively charged small molecules (ATP), while TvTom40-2 and N. crassa Tom40 share both positively and negatively charged patches inside the barrel. The scale of the electrostatic potential ranges from −5 to +5 kT/e.

Jan Tachezy Research Group

Significance

Mitochondria carry out many vital functions in the eukaryotic cells, from energy metabolism to programmed cell death. These organelles descended from bacterial endosymbionts, and during their evolution, the cell established a mechanism to transport nuclear-encoded proteins into mitochondria. Embedded in the mitochondrial outer membrane is a molecular machine, known as the translocase of the outer membrane (TOM) complex, that plays a key role in protein import and biogenesis of the organelle. Here, we provide evidence that the TOM complex of hydrogenosomes, a metabolically specialised anaerobic form of mitochondria in Trichomonas vaginalis, is composed of highly divergent core subunits and lineage-specific peripheral subunits. Despite the evolutionary distance, the T. vaginalis TOM (TvTOM) complex has a conserved triplet-pore structure but with a unique skull-like shape suggesting that the TOM in the early mitochondrion could have formed three pores. Our results contribute to a better understanding of the evolution and adaptation of protein import machinery in anaerobic forms of mitochondria.

Makki, A., Rada, P., Žárský, V., Kereïche, S., Kováčik, L., Novotný, M., Jores, T., Rapaport, D., and Tachezy, J.: Triplet-pore structure of a highly divergent TOM complex of hydrogenosomes in Trichomonas vaginalis, Plos Biol. (2019)17, No. 1, doi.org/10.1371/journal.pbio.3000098