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Nucleic Acids Res. 2015 Jun 23;43(11):5664-72. doi: 10.1093/nar/gkv481. Epub 2015 May 7.

Structure of the nuclease subunit of human mitochondrial RNase P.

Author information

1
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.
2
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.

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.

PMID:
25953853
PMCID:
PMC4477676
DOI:
10.1093/nar/gkv481
[Indexed for MEDLINE]
Free PMC Article

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