title: Crystal structure of RNA-DNA duplex provides insight into conformational changes induced by RNase H binding.
abstract: RNA-DNA hybrids play essential roles in a variety of biological processes, including DNA replication, transcription, and viral integration. Ribonucleotides incorporated within DNA are hydrolyzed by RNase H enzymes in a removal process that is necessary for maintaining genomic stability. In order to understand the structural determinants involved in recognition of a hybrid substrate by RNase H we have determined the crystal structure of a dodecameric non-polypurine/polypyrimidine tract RNA-DNA duplex. A comparison to the same sequence bound to RNase H, reveals structural changes to the duplex that include widening of the major groove to 12.5 Å from 4.2 Å and decreasing the degree of bending along the axis which may play a crucial role in the ribonucleotide recognition and cleavage mechanism within RNase H. This structure allows a direct comparison to be made about the conformational changes induced in RNA-DNA hybrids upon binding to RNase H and may provide insight into how dysfunction in the endonuclease causes disease.
authors: a Department of Biochemistry; Center for Structural Biology ; Wake Forest School of Medicine ; Winston-Salem , NC USA.
authors: Ryan R
authors: RR
authors: Davis
authors: Nadine M
authors: NM
authors: Shaban
authors: Fred W
authors: FW
authors: Perrino
authors: Thomas
authors: T
authors: Hollis
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016914:Ribonuclease H / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D016914:Ribonuclease H
keywords: AGS, Aicardi Goutiéres syndrome; HBD, hybrid binding domain; NMR, nuclear magnetic resonance; PPT, polypyrimidine/polypurine track; RNA-DNA hybrid; RNase H; RNase, ribonuclease; conformational changes; protein nucleic acid interaction