title: Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA.
abstract: Ribonuclease (RNase) P is the universal ribozyme responsible for 5'-end tRNA processing. We report the crystal structure of the Thermotoga maritima RNase P holoenzyme in complex with tRNA(Phe). The 154 kDa complex consists of a large catalytic RNA (P RNA), a small protein cofactor and a mature tRNA. The structure shows that RNA-RNA recognition occurs through shape complementarity, specific intermolecular contacts and base-pairing interactions. Soaks with a pre-tRNA 5' leader sequence with and without metal help to identify the 5' substrate path and potential catalytic metal ions. The protein binds on top of a universally conserved structural module in P RNA and interacts with the leader, but not with the mature tRNA. The active site is composed of phosphate backbone moieties, a universally conserved uridine nucleobase, and at least two catalytically important metal ions. The active site structure and conserved RNase P-tRNA contacts suggest a universal mechanism of catalysis by RNase P.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Reiter
authors.forename: Amy
authors.initials: A
authors.lastname: Osterman
authors.forename: Alfredo
authors.initials: A
authors.lastname: Torres-Larios
authors.forename: Kerren K
authors.initials: KK
authors.lastname: Swinger
authors.forename: Tao
authors.initials: T
authors.lastname: Pan
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mondragón
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005798:Genes, Bacterial / Q000235:genetics; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D012360:RNA, Transfer, Phe / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043262:Ribonuclease P / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology* / Q000235:genetics
chemical_list: D020035:Holoenzymes; D008670:Metals; D012360:RNA, Transfer, Phe; D043262:Ribonuclease P