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 fold of each SUD subdomain is that of a macrodomain ( Figure 2A) . Macrodomains consist of a largely parallel central bsheet surrounded by 4-6 a-helices. The order of regular secondary-structure elements in SUD-N is bN1-aN1-bN2-aN2-bN3-bN4-aN3-bN5-aN4-bN6, and in SUD-M bM1-aM1-bM2-aM2-bM3-bM4-aM3-bM5-aM4-bM6-aM5. The topology of the b-strands is b1-b6-b5-b2-b4-b3, all of which are parallel except b3 (Figure 2A ). Between the two subdomains, most of the secondary-structure elements are conserved with respect to their position in the three-dimensional structure, although they often differ in length. This is particularly obvious for a-helix 1, which comprises just four residues in the N-terminal subdomain but eleven in the M subdomain. Similarly, a-helix 2 has 5 vs. 10 amino-acid residues in the two subdomains. In general, the strands of the central b-sheet appear to align better between the two subdomains than do the a-helices.