EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Loop-mediated regulation and base flipping drive RNA cleavage by human mitochondrial PNPase.
ジャーナル・号・ページ	Nucleic Acids Res, Vol. 53, Issue 22, Year 2025
掲載日	2025年11月26日
著者	Ole Unseld / Hrishikesh Das / B Martin Hällberg /
PubMed 要旨	Human polynucleotide phosphorylase (hPNPase), a trimeric exoribonuclease, is crucial for maintaining mitochondrial RNA metabolism, including the regulated degradation of RNA. Mutations in hPNPase ...Human polynucleotide phosphorylase (hPNPase), a trimeric exoribonuclease, is crucial for maintaining mitochondrial RNA metabolism, including the regulated degradation of RNA. Mutations in hPNPase have been linked to mitochondrial pathologies, underscoring its importance in mitochondrial RNA homeostasis. Despite this significance, the molecular basis of its catalytic mechanism and the structural consequences of active-site mutations remain poorly understood. We employed high-resolution electron cryo-microscopy to capture three distinct functional states of hPNPase during RNA degradation. In the loading state, flexible loops facilitate the recruitment of the substrate RNA and guide it toward the active site. During the pre-catalytic state, terminal nucleotides reorient within the active site, positioning the RNA backbone for cleavage, which is stabilized by Mg2+. Finally, the catalytic state reveals a nucleophilic attack of phosphate on the RNA backbone, mediated by key active-site residues. These results offer a clear biochemical framework for hPNPase-mediated RNA turnover, clarifying its catalytic mechanism and highlighting how active-site integrity is crucial for efficient RNA degradation.
リンク	Nucleic Acids Res / PubMed:41361968 / PubMed Central
手法	EM (単粒子)
解像度	2.08 - 2.65 Å
構造データ	49478 9njb EMDB-49478, PDB-9njb: hPNPase RNA pre-catalytic state 手法: EM (単粒子) / 解像度: 2.15 Å 49479 9njc EMDB-49479, PDB-9njc: hPNPase bound to PO4 in loop conformation 1 手法: EM (単粒子) / 解像度: 2.36 Å 49480 9njd EMDB-49480, PDB-9njd: hPNPase bound to PO4 in loop conformation 3 手法: EM (単粒子) / 解像度: 2.44 Å 49481 9nje EMDB-49481, PDB-9nje: hPNPase bound to PO4 in loop conformation 2 手法: EM (単粒子) / 解像度: 2.44 Å 49590 9no0 EMDB-49590, PDB-9no0: hPNPase RNA loading state 手法: EM (単粒子) / 解像度: 2.08 Å 72335 9xyi EMDB-72335, PDB-9xyi: hPNPase RNA loading state 手法: EM (単粒子) / 解像度: 2.46 Å 72352 9xzf EMDB-72352, PDB-9xzf: hPNPase RNA loading state with extended RNA in the bottom 手法: EM (単粒子) / 解像度: 2.65 Å
化合物	ChemComp-SO4: SULFATE ION / 硫酸ジアニオン ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-PO4: PHOSPHATE ION / ホスファ-ト
由来	homo sapiens (ヒト)
キーワード	RNA BINDING PROTEIN/RNA / RNase / Protein-RNA Complex / RNA degradation / mitochondria / phosphorolytic enzyme / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex / PO4 binding / TRANSFERASE/RNA / TRANSFERASE-RNA complex