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. 2018 Mar 22;14(3):e1006864.
doi: 10.1371/journal.ppat.1006864. eCollection 2018 Mar.

Macrodomain ADP-ribosylhydrolase and the pathogenesis of infectious diseases

Anthony K L Leung  1   2 , Robert Lyle McPherson  1 , Diane E Griffin  3
Affiliations

Macrodomain ADP-ribosylhydrolase and the pathogenesis of infectious diseases

Anthony K L Leung et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. A brief timeline of the discovery of macrodomain functions.
Significant advances in the macrodomain field starting from the initial identification of “X-domains” in coronaviruses by Lee et al. in 1991 [4] to the present. Findings are listed in bold followed by relevant citations.
Fig 2
Fig 2. 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.
Fig 3
Fig 3. Model: ADP-ribosylation at the forefront of the battle between the virus and the host.
A working model based on (1) ADP-ribosylation and host PARPs induced upon virus infection/interferon and (2) viral macrodomain possession of ADP-ribosylhydrolase activity. ADP-ribose can be conjugated to amino acids of diverse chemistry (Asp, Glu, Lys, Arg, Ser, and Cys). MacroD-type macrodomain, to which viral macrodomain belong, removes ADP-ribose conjugated to Asp and Glu, but not Lys and Ser. The ability of viral macrodomains to hydrolyze ADP-ribose from Arg and Cys remains unclear. ADP-ribose, adenosine diphosphate ribose; Arg, arginine; Asp, aspartic acid; Cys, cysteine; Glu, glutamic acid; Lys, lysine; PARP, poly(ADP-ribose) polymerase; Ser, serine.
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References

    1. Rack JGM, Perina D, Ahel I. Macrodomains: Structure, Function, Evolution, and Catalytic Activities. Annu Rev Biochem. 2016. doi: 10.1146/annurev-biochem-060815-014935 - DOI - PubMed
    1. Feijs KLH, Forst AH, Verheugd P, Lüscher B. Macrodomain-containing proteins: regulating new intracellular functions of mono(ADP-ribosyl)ation. Nat Rev Mol Cell Biol. 2013;14: 445–453. doi: 10.1038/nrm3601 - DOI - PMC - PubMed
    1. Barkauskaite E, Jankevicius G, Ladurner AG, Ahel I, Timinszky G. The recognition and removal of cellular poly(ADP-ribose) signals. FEBS J. 2013;280: 3491–3507. doi: 10.1111/febs.12358 - DOI - PubMed
    1. Lee HJ, Shieh CK, Gorbalenya AE, Koonin EV, La Monica N, Tuler J, et al. The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase. Virology. 1991;180: 567–582. - PMC - PubMed
    1. Pehrson JR, Fuji RN. Evolutionary conservation of histone macroH2A subtypes and domains. Nucleic Acids Res. 1998;26: 2837–2842. - PMC - PubMed

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