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

In both crystal forms, SUD core displays the same head-to-tail dimer, with the SUD-N subdomain of monomer A interacting with the SUD-M subdomain of monomer B, and vice versa. Approximately 1130 Å 2 of solvent-accessible surface per monomer is buried upon dimerization ( Figure 3 ). Due to the two-domain architecture of each monomer, the resulting four lobes give the dimer a quasi-tetrahedral shape ( Figure 3A ). Involving ,10 hydrogen bonds and four well-defined salt-bridges (As-pB440…ArgA554, ArgB473…GluA619, ArgB554…AspA440, and GluB619…ArgA473), interactions between the monomers are largely hydrophilic. As to be expected, the structures of the monomers are very similar to one another, with r.m.s.d. values (for Ca atoms) of 0.58 Å between monomers A and B of the monoclinic crystal form, and 0.11-0.37 Å between monomers A-D of the triclinic form. The structure of SUD-M alone is even better conserved between the individual copies of SUD core . Also, the fold of the SUD-M subdomain is similar to the model of the SUD fragment 527-651 derived from NMR measurements, which was published very recently (r.m.s.d. ,0.9 Å ) [29] .