In Nature this week, researchers in the US and UK report on an influenza histone mimic that can suppress antiviral response. The team describes a novel mechanism through which an influenza virus can affect host cells through the interaction of the cell's epigenome with influenza non-structural protein 1. "We show that the NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by the virus to target the human PAF1 transcription elongation complex (hPAF1C)," the authors write. "We demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and results in suppression of hPAF1C-mediated transcriptional elongation. Furthermore, human PAF1 has a crucial role in the antiviral response." Loss of hPAF1C binding by this mechanism helps the influenza infection spread, the team adds.
Published online in Nature this week, a team of European and American researchers describe the crystal structure of the 2.8 Å crystal structure of the mouse µ-opioid receptor in complex with an irreversible morphinan antagonist. "Of particular interest, the µ-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6," the authors write. "These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction."
Researchers at the Institute of Cancer Research in the UK describe the structure of the mitotic checkpoint complex in Nature this week. Using the crystal structure of Schizosaccharomyces pombe's mitotic checkpoint complex, the team shows the molecular basis of mitotic checkpoint complex-mediated anaphase-promoting complex/cyclosome inhibition. "The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10," the authors write. "Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31comet (also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31comet disrupts MCC assembly to antagonize the [spindle assembly checkpoint.]"