title: The macro domain is an ADP-ribose binding module.
abstract: The ADP-ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, transcription, chromatin biology and long-term memory formation. Yet no protein modules are known that specifically recognize the ADP-ribose nucleotide. We provide biochemical and structural evidence that macro domains are high-affinity ADP-ribose binding modules. Our structural analysis reveals a conserved ligand binding pocket among the macro domain fold. Consistently, distinct human macro domains retain their ability to bind ADP-ribose. In addition, some macro domain proteins also recognize poly-ADP-ribose as a ligand. Our data suggest an important role for proteins containing macro domains in the biology of ADP-ribose.
authors.affiliation: Gene Expression Programme and Structural & Computational Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Karras
authors.forename: Georg
authors.initials: G
authors.lastname: Kustatscher
authors.forename: Heeran R
authors.initials: HR
authors.lastname: Buhecha
authors.forename: Mark D
authors.initials: MD
authors.lastname: Allen
authors.forename: Céline
authors.initials: C
authors.lastname: Pugieux
authors.forename: Fiona
authors.initials: F
authors.lastname: Sait
authors.forename: Mark
authors.initials: M
authors.lastname: Bycroft
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Ladurner
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D019611:Archaeoglobus fulgidus / Q000737:chemistry*; D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D019843:Archaeal Proteins; D002352:Carrier Proteins; D006657:Histones; D008024:Ligands; D009363:Neoplasm Proteins; C418133:PARP9 protein, human; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; D000244:Adenosine Diphosphate; D011065:Poly(ADP-ribose) Polymerases; C496851:Poa1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases