School of Biological Sciences, Nanyang Technological University, Singapore, Republic of Singapore.
FEBS Lett. 2021 Dec;595(24):3006-3018. doi: 10.1002/1873-3468.14236. Epub 2021 Nov 27.
The stringent response is critical for the survival of Mycobacterium tuberculosis (Mtb) under nutrient starvation. The mechanism is mediated by a GTP pyrophosphokinase known as Rel, containing N-terminal synthetase and hydrolase domains and C-terminal regulatory domains, which include the TGS domain (ThrRS, GTPase, and SpoT proteins) that has been proposed to activate the synthetase domain via interaction with deacylated tRNA. Here, we present the NMR solution structure of the Mtb Rel TGS domain (MtRel TGS), consisting of five antiparallel β-strands and one helix-loop-helix motif. The interaction of MtRel TGS with deacylated tRNA is shown, indicating the critical amino acids of MtRel TGS in tRNA binding, and presenting the first structural evidence of MtRel TGS binding to deacylated tRNA in solution in the absence of the translational machinery.
严格的反应对于分枝杆菌（Mycobacterium tuberculosis，Mtb）在营养饥饿下的生存至关重要。这种机制是由一种称为 Rel 的 GTP 焦磷酸激酶介导的，它包含 N 端合成酶和水解酶结构域以及 C 端调节结构域，其中包括 TGS 结构域（ThrRS、GTPase 和 SpoT 蛋白），该结构域被提议通过与去酰化 tRNA 的相互作用来激活合成酶结构域。在这里，我们展示了 Mtb Rel TGS 结构域（MtRel TGS）的 NMR 溶液结构，由五个反平行的β-折叠和一个螺旋-环-螺旋基序组成。展示了 MtRel TGS 与去酰化 tRNA 的相互作用，表明了 MtRel TGS 在 tRNA 结合中的关键氨基酸，并提供了在翻译机制不存在的情况下，MtRel TGS 在溶液中与去酰化 tRNA 结合的第一个结构证据。
