ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Structural basis of RNA processing by human mitochondrial RNase P. 著者: Arjun Bhatta / Christian Dienemann / Patrick Cramer / Hauke S Hillen / 要旨: Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In ...Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria.
根拠: gel filtration, In-vitro reconstitution of the complex from recombinant subunits and gel filtration performed by us and others (Oerum et al. 2018) supports mtRNase P complex assembly.
タイプ
名称
対称操作
数
identity operation
1_555
1
Buried area
33180 Å2
ΔGint
-237 kcal/mol
Surface area
74250 Å2
手法
PISA
-
要素
-
タンパク質 , 2種, 5分子 ABCDF
#1: タンパク質
3-hydroxyacyl-CoAdehydrogenasetype-2 / 17-beta-estradiol 17-dehydrogenase / 2-methyl-3-hydroxybutyryl-CoA dehydrogenase / MHBD / 3-alpha- ...17-beta-estradiol 17-dehydrogenase / 2-methyl-3-hydroxybutyryl-CoA dehydrogenase / MHBD / 3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)) / 3-hydroxy-2-methylbutyryl-CoA dehydrogenase / 3-hydroxyacyl-CoA dehydrogenase type II / 3alpha(or 20beta)-hydroxysteroid dehydrogenase / 7-alpha-hydroxysteroid dehydrogenase / Endoplasmic reticulum-associated amyloid beta-peptide-binding protein / Mitochondrial ribonuclease P protein 2 / Mitochondrial RNase P protein 2 / Short chain dehydrogenase/reductase family 5C member 1 / Short-chain type dehydrogenase/reductase XH98G2 / Type II HADH
MitochondrialribonucleasePcatalyticsubunit / Mitochondrial ribonuclease P protein 3 / Mitochondrial RNase P protein 3 / Protein only RNase P ...Mitochondrial ribonuclease P protein 3 / Mitochondrial RNase P protein 3 / Protein only RNase P catalytic subunit