title: Crystal structure of RNase H3-substrate complex reveals parallel evolution of RNA/DNA hybrid recognition.
abstract: RNases H participate in the replication and maintenance of genomic DNA. RNase H1 cleaves the RNA strand of RNA/DNA hybrids, and RNase H2 in addition hydrolyzes the RNA residue of RNA-DNA junctions. RNase H3 is structurally closely related to RNases H2, but its biochemical properties are similar to type 1 enzymes. Its unique N-terminal substrate-binding domain (N-domain) is related to TATA-binding protein. Here, we report the first crystal structure of RNase H3 in complex with its RNA/DNA substrate. Just like RNases H1, type 3 enzyme recognizes the 2'-OH groups of the RNA strand and detects the DNA strand by binding a phosphate group and inducing B-form conformation. Moreover, the N-domain recognizes RNA and DNA in a manner that is highly similar to the hybrid-binding domain of RNases H1. Our structure demonstrates a remarkable example of parallel evolution of the elements used in the specific recognition of RNA and DNA.
authors.affiliation: Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, 4 Trojdena Street, 02-109 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Figiel
authors.affiliation: Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, 4 Trojdena Street, 02-109 Warsaw, Poland mnowotny@iimcb.gov.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Nowotny
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016914:Ribonuclease H / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D012313:RNA; D004247:DNA; D016914:Ribonuclease H