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

The idea that coronaviral X-domains might function as modules binding poly(ADP-ribose) [23] received support from the observation that some macrodomains are connected with domains showing poly(ADP-ribose) polymerase (PARP) activity, i.e. in the so-called macroPARPs (PARP-9 and PARP-14) [49] . There are 18 human genes for members of the PARP family; the prototype enzyme, PARP-1, catalyzes the post-translational modification of many substrate proteins, including itself, in a multitude of cellular processes (DNA repair, transcriptional regulation, energy metabolism, and apoptosis) [50] [51] [52] . Interestingly, SUD-M and the C-terminal 74-residue subdomain (SUD-C) that is missing in our SUD core construct together show a ,15% sequence identity (32% similarity) to the catalytic domain of PARP-1. However, the three-dimensional structures of SUD-M (this work) and the C-terminal domain of PARP-1 [53] are different and cannot be superimposed. Another feature common between SARS-CoV SUD and PARP-1 is that the latter has recently been shown to bind to G-quadruplexes [54] , although it is generally assumed that this occurs through the DNA-binding domain rather than the catalytic domain of PARP-1.