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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Diphosphate / metabolism
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Adenosine Diphosphate Ribose / metabolism*
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Amino Acid Sequence
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Archaeal Proteins / chemistry*
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Archaeal Proteins / metabolism
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Archaeoglobus fulgidus / chemistry*
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Binding Sites
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Calorimetry, Differential Scanning
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Catalysis
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Crystallography, X-Ray
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Histones / chemistry
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Histones / metabolism
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Humans
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Hydrolysis
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Ligands
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Models, Molecular
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Molecular Sequence Data
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism
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Phosphoric Monoester Hydrolases / chemistry
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Phosphoric Monoester Hydrolases / metabolism
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Poly Adenosine Diphosphate Ribose / metabolism
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Poly(ADP-ribose) Polymerases
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Species Specificity
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Structure-Activity Relationship
Substances
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Archaeal Proteins
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Carrier Proteins
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Histones
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Ligands
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Neoplasm Proteins
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PARP9 protein, human
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Adenosine Diphosphate Ribose
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Poly Adenosine Diphosphate Ribose
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Adenosine Diphosphate
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Poly(ADP-ribose) Polymerases
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Poa1 protein, S cerevisiae
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Phosphoric Monoester Hydrolases