Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease
Figure 5
Modeling and mutational analysis suggest that PLpro binds to ISG15 and K48-Ub2, but not K63-Ub2, in a bidentate manner.
Initial model of PLpro (blue surface) bound to ISG15 (yellow) (A), K48-Ub2 (orange) (B), and K63-Ub2 (orange) (C). The multiple conformations of the distal ubiquitin depicted as transparent cartoons in (B) represent the range of pre-experimental binding configurations for K48-Ub2. D. A detailed view of mutated PLpro residues designed to locate the second binding site for K48-Ub2 and ISG15. These residues are shaded in cyan in A–D. Residues marked with an asterisk designate follow-up mutations.