title: Macrodomains: Structure, Function, Evolution, and Catalytic Activities.
abstract: Recent developments indicate that macrodomains, an ancient and diverse protein domain family, are key players in the recognition, interpretation, and turnover of ADP-ribose (ADPr) signaling. Crucial to this is the ability of macrodomains to recognize ADPr either directly, in the form of a metabolic derivative, or as a modification covalently bound to proteins. Thus, macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Their importance is further indicated by the fact that dysregulation or mutation of a macrodomain is associated with several diseases, including cancer, developmental defects, and neurodegeneration. In this review, we summarize the current insights into macrodomain evolution and how this evolution influenced their structural and functional diversification. We highlight some aspects of macrodomain roles in pathobiology as well as their emerging potential as therapeutic targets.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; email: johannes.rack@path.ox.ac.uk , ivan.ahel@path.ox.ac.uk.
authors: Johannes Gregor Matthias
authors: JG
authors: Rack
authors: Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10002, Croatia; email: drago.Perina@irb.hr.
authors: Dragutin
authors: D
authors: Perina
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; email: johannes.rack@path.ox.ac.uk , ivan.ahel@path.ox.ac.uk.
authors: Ivan
authors: I
authors: Ahel
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D009369:Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010802:Phylogeny; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D040681:Structural Homology, Protein; D014777:Virus Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D029968:Escherichia coli Proteins; D007527:Isoenzymes; C504447:ParG protein, E coli; D012097:Repressor Proteins; D000246:Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases
keywords: ADP-ribose; NAD; PARG; PARP family; posttranslational modifications