title: Structure of the nuclease subunit of human mitochondrial RNase P.
abstract: Mitochondrial RNA polymerase produces long polycistronic precursors that contain the mRNAs, rRNAs and tRNAs needed for mitochondrial translation. Mitochondrial RNase P (mt-RNase P) initiates the maturation of the precursors by cleaving at the 5' ends of the tRNAs. Human mt-RNase P is only active as a tripartite complex (mitochondrial RNase P proteins 1-3; MRPP1-3), whereas plant and trypanosomal RNase Ps (PRORPs)-albeit homologous to MRPP3-are active as single proteins. The reason for this discrepancy has so far remained obscure. Here, we present the crystal structure of human MRPP3, which features a remarkably distorted and hence non-productive active site that we propose will switch to a fully productive state only upon association with MRPP1, MRPP2 and pre-tRNA substrate. We suggest a mechanism in which MRPP1 and MRPP2 both deliver the pre-tRNA substrate and activate MRPP3 through an induced-fit process.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden Röntgen-Ångström-Cluster, Karolinska Institutet Outstation, Centre for Structural Systems Biology, DESY-Campus, 22607 Hamburg, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Reinhard
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden Röntgen-Ångström-Cluster, Karolinska Institutet Outstation, Centre for Structural Systems Biology, DESY-Campus, 22607 Hamburg, Germany.
authors.forename: Sagar
authors.initials: S
authors.lastname: Sridhara
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden Röntgen-Ångström-Cluster, Karolinska Institutet Outstation, Centre for Structural Systems Biology, DESY-Campus, 22607 Hamburg, Germany European Molecular Biology Laboratory, Hamburg Unit, 22603 Hamburg, Germany Martin.Hallberg@ki.se.
authors.forename: B Martin
authors.initials: BM
authors.lastname: Hällberg
mesh_terms: D029681:Arabidopsis Proteins / Q000737:chemistry; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D043262:Ribonuclease P / Q000737:chemistry*
chemical_list: D029681:Arabidopsis Proteins; D021122:Protein Subunits; C545252:PRORP protein, human; C581753:PRORP1 protein, Arabidopsis; D043262:Ribonuclease P