7SP3

E. coli RppH bound to Ap4A

7SP3 の概要

• エントリーDOI: 10.2210/pdb7sp3/pdb
• 分子名称: RNA pyrophosphohydrolase, BIS(ADENOSINE)-5'-TETRAPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: cap, ap4a, rpph, nudix hydrolase, rna binding protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19929.53

構造登録者

Serganov, A.A.,Vasilyev, N.,Nuthanakanti, A. (登録日: 2021-11-02, 公開日: 2022-03-09, 最終更新日: 2023-10-18)

主引用文献

Levenson-Palmer, R.,Luciano, D.J.,Vasilyev, N.,Nuthanakanti, A.,Serganov, A.,Belasco, J.G.
A distinct RNA recognition mechanism governs Np 4 decapping by RppH.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: Dinucleoside tetraphosphates, often described as alarmones because their cellular concentration increases in response to stress, have recently been shown to function in bacteria as precursors to nucleoside tetraphosphate (Np) RNA caps. Removal of this cap is critical for initiating 5' end-dependent degradation of those RNAs, potentially affecting bacterial adaptability to stress; however, the predominant Np decapping enzyme in proteobacteria, ApaH, is inactivated by the very conditions of disulfide stress that enable Np-capped RNAs to accumulate to high levels. Here, we show that, in cells experiencing such stress, the RNA pyrophosphohydrolase RppH assumes a leading role in decapping those transcripts, preferring them as substrates over their triphosphorylated and diphosphorylated counterparts. Unexpectedly, this enzyme recognizes Np-capped 5' ends by a mechanism distinct from the one it uses to recognize other 5' termini, resulting in a one-nucleotide shift in substrate specificity. The unique manner in which capped substrates of this kind bind to the active site of RppH positions the δ-phosphate, rather than the β-phosphate, for hydrolytic attack, generating triphosphorylated RNA as the primary product of decapping. Consequently, a second RppH-catalyzed deprotection step is required to produce the monophosphorylated 5' terminus needed to stimulate rapid RNA decay. The unconventional manner in which RppH recognizes Np-capped 5' ends and its differential impact on the rates at which such termini are deprotected as a prelude to RNA degradation could have major consequences for reprogramming gene expression during disulfide stress.

PubMed: 35131855
DOI: 10.1073/pnas.2117318119

実験手法

X-RAY DIFFRACTION (1.6 Å)