6G0Z

Crystal structure of GDP bound RbgA from S. aureus

6G0Z の概要

• エントリーDOI: 10.2210/pdb6g0z/pdb
• 分子名称: Ribosome biogenesis GTPase A, GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: cpgtpase, rna binding protein
• 由来する生物種: Staphylococcus aureus (strain USA300)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69519.70

構造登録者

Pausch, P.,Bange, G. (登録日: 2018-03-20, 公開日: 2018-11-07, 最終更新日: 2024-01-17)

主引用文献

Pausch, P.,Steinchen, W.,Wieland, M.,Klaus, T.,Freibert, S.A.,Altegoer, F.,Wilson, D.N.,Bange, G.
Structural basis for (p)ppGpp-mediated inhibition of the GTPase RbgA.
J. Biol. Chem., 293:19699-19709, 2018

PubMed Abstract: Efficient adaptation to environmental changes is pivotal for all bacterial cells. Almost all bacterial species depend on the conserved stringent response system to prompt timely transcriptional and metabolic responses according to stress conditions and nutrient depletion. The stringent response relies on the stress-dependent synthesis of the second messenger nucleotides and alarmones (p)ppGpp, which pleiotropically target and reprogram processes that consume cellular resources, such as ribosome biogenesis. Here we show that (p)ppGpp acts on the ribosome biogenesis GTPase A (RbgA) of Gram-positive bacteria. Using X-ray crystallography, hydrogen-deuterium exchange MS (HDX-MS) and kinetic analysis, we demonstrate that the alarmones (p)ppGpp bind to RbgA in a manner similar to that of binding by GDP and GTP and thereby act as competitive inhibitors. Our structural analysis of RbgA bound to ppGpp and pppGpp at 1.8 and 1.65 Å resolution, respectively, suggested that the alarmones (p)ppGpp prevent the active GTPase conformation of RbgA by sterically blocking the association of its G2 motif via their 3'-pyrophosphate moieties. Taken together, our structural and biochemical characterization of RbgA in the context of the alarmone-mediated stringent response reveals how (p)ppGpp affects the function of RbgA and reprograms this GTPase to arrest the ribosomal large subunit.

PubMed: 30366986
DOI: 10.1074/jbc.RA118.003070

実験手法

X-RAY DIFFRACTION (2.15 Å)