title: Structure of the Methanothermobacter thermautotrophicus exosome RNase PH ring.
abstract: The core of the exosome, a versatile multisubunit RNA-processing enzyme found in archaea and eukaryotes, includes a ring of six RNase PH subunits. This basic architecture is homologous to those of the bacterial and archaeal RNase PHs and the bacterial polynucleotide phosphorylase (PNPase). While all six RNase PH monomers are catalytically active in the homohexameric RNase PH, only half of them are functional in the bacterial PNPase and in the archaeal exosome core and none are functional in the yeast and human exosome cores. Here, the crystal structure of the RNase PH ring from the exosome of the anaerobic methanogenic archaeon Methanothermobacter thermautotrophicus is described at 2.65 A resolution. Free phosphate anions were found for the first time in the active sites of the RNase PH subunits of an exosome structure and provide structural snapshots of a critical intermediate in the phosphorolytic degradation of RNA by the exosome. Furthermore, the present structure highlights the plasticity of the surfaces delineating the polar regions of the RNase PH ring of the exosome, a feature that can facilitate both interaction with the many cofactors involved in exosome function and the processive activity of this enzyme.
authors.affiliation: York Structural Biology Laboratory, Chemistry Department, University of York, York YO10 5YW, England. clng@mrc-lmb.cam.ac.uk
authors.forename: C Leong
authors.initials: CL
authors.lastname: Ng
authors.forename: David G
authors.initials: DG
authors.lastname: Waterman
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Antson
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortiz-Lombardía
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D017013:Methanobacteriaceae / Q000201:enzymology*; D008958:Models, Molecular; D010710:Phosphates / Q000378:metabolism; D011485:Protein Binding; D012260:Ribonucleases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010710:Phosphates; D012260:Ribonucleases