Among six human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle-East respiratory syndrome coronavirus (MERSCoV) are connected with severe respiratory-tract infection, which lead to high case-fatality rates of ~10 and ~35%, respectively. The papain-like protease, a domain located in the middle part of the largest non-structural protein Nsp3, has proteolytic, deubiquitinating, and deISGylating activities. The latter two functions are involved in the suppression of the antiviral innate immune response of the host cell. In this issue, Lei and Hilgenfeld present the X-ray crystal structure of a complex between MERS-CoV PLpro and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. The cover shows five regions of the PLpro bind to two areas of the Ub. See page 288-299 for details.