Structure and functions of viral macrodomains.

(A) Ribbon representation of CHIKV nsP3 macrodomain (PDB: 3GPO, Malet et al. 2009 J Virol) in complex with ADP-ribose ligand. Conserved structural motifs critical for ligand recognition are highlighted in color and functionally conserved residues frequently mutated in studies of viral macrodomains are represented as sticks. (B) Phenotypes of macrodomain mutant viruses characterized in cells and in vivo. Corresponding residues and regions across different viruses are color-coded in panels a and b. ADP-ribose, adenosine diphosphate ribose; CHIKV, Chikungunya virus; PDB, Protein Data Bank.