Structure of the nuclease subunit of human mitochondrial RNase P
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 activ...
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| Veröffentlicht in: | Nucleic acids research 2015-06, Vol.43 (11), p.5664-5672 |
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| creator | Reinhard, Linda Sridhara, Sagar Hällberg, B Martin |
| description | 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. |
| doi_str_mv | 10.1093/nar/gkv481 |
| format | Article |
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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. 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| source | Oxford Journals Open Access Collection; MEDLINE; PubMed Central; Directory of Open Access Journals; SWEPUB Freely available online; Free Full-Text Journals in Chemistry |
| subjects | Arabidopsis Proteins - chemistry Catalytic Domain Humans Models, Molecular Protein Structure, Tertiary Protein Subunits - chemistry Ribonuclease P - chemistry Structural Biology |
| title | Structure of the nuclease subunit of human mitochondrial RNase P |
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