title: Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination.
abstract: Protein poly(ADP-ribosyl)ation and ubiquitination are two key post-translational modifications regulating many biological processes. Through crystallographic and biochemical analysis, we show that the RNF146 WWE domain recognizes poly(ADP-ribose) (PAR) by interacting with iso-ADP-ribose (iso-ADPR), the smallest internal PAR structural unit containing the characteristic ribose-ribose glycosidic bond formed during poly(ADP-ribosyl)ation. The key iso-ADPR-binding residues we identified are highly conserved among WWE domains. Binding assays further demonstrate that PAR binding is a common function for the WWE domain family. Since many WWE domain-containing proteins are known E3 ubiquitin ligases, our results suggest that protein poly(ADP-ribosyl)ation may be a general mechanism to target proteins for ubiquitination.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Michaud
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hinds
authors.forename: Erkang
authors.initials: E
authors.lastname: Fan
authors.forename: Feng
authors.initials: F
authors.lastname: Cong
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xu
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; C561932:RNF146 protein, human; D044767:Ubiquitin-Protein Ligases