The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Tan, Jinzhi; Vonrhein, Clemens; Smart, Oliver S.; Bricogne, Gerard; Bollati, Michela; Kusov, Yuri; Hansen, Guido; Mesters, Jeroen R.; Schmidt, Christian L.; Hilgenfeld, Rolf

Among the subdomains of the Nsp3 multidomain protein, there is also the so-called ''X-domain'' (Nsp3b), which shows structural homology to macrodomains. The latter name refers to the nonhistone-like domain of the histone macro2A [17] [18] [19] . In animal cells, such domains are occasionally physically associated with enzymes involved in ADP-ribosylation or ADP-ribose metabolism. Because of this linkage and on the basis of sequence similarity to Poa1p, a yeast protein involved in the removal of the 10-phosphate group from ADP-ribose 10-phosphate (a late step in tRNA splicing; [20] ), it has been proposed that the coronaviral X-domains may have the function of ADP-ribose-10-phosphatases (ADRPs; [21] ). The crystal structures of X-domains of SARS-CoV [22, 23] as well as of HCoV 229E and Infectious Bronchitis Virus (IBV) [24] show that the protein has the three-layer a/b/a fold characteristic of the macrodomains.