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A-form DNA for survival

Credit: DiMaio et al., Science (2015)

SIRV2 is a double-stranded DNA virus that infects Sulfolobus islandicus, an archaeon that lives in an environment with temperatures around 80 oC and a pH of 3. Egelman, Prangishvili and colleagues have now investigated how SIRV2 maintains its genomic integrity under such extreme conditions. The rod-shaped virion was known to be composed of thousands of copies of a small DNA–binding capsid protein. Using cryo-EM and comparative modeling (RosettaCM), the researchers reconstructed the structure of the SIRV2 virion at 4-Å resolution. The structure revealed that the DNA is in A form and is encapsulated by the N-terminal portion of the capsid protein, which is unstructured in solution but folded into helix-turn-helix motifs in the virion. The helices from neighboring protein subunits are packed in an antiparallel, interdigitated arrangement, and they wrap tightly around the DNA, interacting with the phosphate backbone via conserved polar and hydrophobic residues. Along with hydrophobic interprotein interactions, this arrangement keeps the DNA completely surrounded by protein and inaccessible to solvent. These features are reminiscent of early observations on the Bacillus subtilis spore, a dormant form of the bacterium that shows high resistance to heat, radiation, chemical treatments and desiccation. Within B. subtilis spores, the genomic DNA is in complex with small acid-soluble proteins (SASPs), which can induce a transition of double-stranded DNA from B to A form in vitro. SASPs and SIRV2 protein share no detectable sequence or structural homology, and the functional convergence indicates that adopting A-form DNA might be a widespread biological mechanism allowing organisms to withstand adverse conditions. (Science 348, 914–917, 2015)

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Chen, I. A-form DNA for survival. Nat Struct Mol Biol 22, 441 (2015). https://doi.org/10.1038/nsmb.3045

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