Structural biology

Structure of the outer membrane complex of a type IV secretion system Chandran, V. et al. Nature 462, 1011–1015 (2009)

Writing in Nature, Chandran, Fronzes and colleagues report the first crystal structure of a type IV secretion system (T4SS) outer-membrane complex: that of the conjugative plasmid pKM101. Unexpectedly, the 2.6 Å resolution structure revealed that the outer-membrane pore is formed solely by the VirB10 homologue TraF rather than by the VirB9 homologue TraO, as had been predicted. The pore itself is an unusual structure formed by a two-helix bundle ring system. The authors use information from the crystal structure and previous cryo-electron microscopy data to propose a model for how the pore opens and closes. At 590 kDa, this is the largest outer-membrane protein complex for which the crystal structure has been solved.

Evolution

Giant Marseillevirus highlights the role of amoebae as a melting pot in emergence of chimeric microorganisms Boyer, M. et al. Proc. Natl Acad. Sci. USA 106, 21848–21853 (2009)

The discovery of Mimivirus (the largest virus isolated to date, with viral particles that are large enough to be seen with the light microscope) began to change our understanding of what constitutes a virus. A recent paper reports the isolation of another giant virus from an amoeba host. Marseillevirus has a genome of 368 kb and forms viral particles that are 250 nm in diameter. Sequence comparisons and phylogenetic analyses revealed that Marseillevirus belongs to a new family of nucleocytoplasmic large DNA viruses and that the 457 predicted genes in its genome have been acquired from several sources, including eukaryotes, amoebae and bacteria. Amoebae are host to a range of microorganisms, and the authors propose that amoebae function as “a veritable factory for gene mixing between the eukaryotic host, its various viruses, and bacterial parasites and symbionts.”

Bacterial physiology

Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli Davies, B. W. et al. Mol. Cell 36, 845–860 (2009)

Hydroxyurea (HU) is known to cause replication fork arrest by depleting deoxyribonucleotide triphosphate (dNTP) pools through the inhibition of class I ribonucleotide reductase, but how this leads to cell death was unknown. Bryan Davies and colleagues present a detailed analysis of the mechanism of HU-induced cell death in Escherichia coli. HU stress leads to the upregulation of cell survival pathways and also increases iron uptake, which the authors showed was involved in cell death by causing the generation of hydroxyl radicals. However, this was not the whole story, and further analysis revealed the unexpected involvement of the toxins MazF and RelE. The authors propose a detailed model in which activation of MazF and RelE, in response to dNTP depletion after prolonged HU exposure, leads to the accumulation of incorrectly translated proteins and the subsequent activation of membrane stress responses, which disrupts respiratory chain activity. This increases superoxide production, which, in conjunction with the increased iron uptake, leads to the generation of hydroxyl radicals and cell death.