A recent paper from the Walden and Shaw labs, published in the EMBO Journal, reported the mechanism of inhibition and allosteric activation of Parkin, an important ubiquitin ligase mutated in Parkinson's disease. When the activation signal phosphoubiquitin binds to Parkin, the inhibitory domain is ejected from a distant site to reveal a surface required for Parkin to engage with components of the ubiquitin-conjugating machinery. Many of the disease-causing mutations in Parkin disrupt this fine balance between inhibited and activated Parkin.

The work was published online in EMBO Journal in August (followed the next month by a News & Views piece discussing the findings) and published in print (vol.34 issue 20) today, with an image depicting the dynamic rearrangements that occur to transition Parkin from an inhibited to active state chosen as the cover image.