Seely Savannah M, Basu Ritwika S, Gagnon Matthieu G
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Nucleic Acids Res. 2024 Apr 24;52(7):4053-4066. doi: 10.1093/nar/gkae128.
During stress conditions such as heat shock and antibiotic exposure, ribosomes stall on messenger RNAs, leading to inhibition of protein synthesis. To remobilize ribosomes, bacteria use rescue factors such as HflXr, a homolog of the conserved housekeeping GTPase HflX that catalyzes the dissociation of translationally inactive ribosomes into individual subunits. Here we use time-resolved cryo-electron microscopy to elucidate the mechanism of ribosome recycling by Listeria monocytogenes HflXr. Within the 70S ribosome, HflXr displaces helix H69 of the 50S subunit and induces long-range movements of the platform domain of the 30S subunit, disrupting inter-subunit bridges B2b, B2c, B4, B7a and B7b. Our findings unveil a unique ribosome recycling strategy by HflXr which is distinct from that mediated by RRF and EF-G. The resemblance between HflXr and housekeeping HflX suggests that the alternative ribosome recycling mechanism reported here is universal in the prokaryotic kingdom.
在诸如热休克和抗生素暴露等应激条件下，核糖体在信使核糖核酸（mRNA）上停滞，导致蛋白质合成受到抑制。为了重新激活核糖体，细菌会利用诸如HflXr等拯救因子，HflXr是保守的管家GTP酶HflX的同源物，它催化翻译无活性的核糖体解离成单个亚基。在这里，我们使用时间分辨冷冻电子显微镜来阐明单核细胞增生李斯特菌HflXr进行核糖体循环利用的机制。在70S核糖体中，HflXr取代了50S亚基的H69螺旋，并诱导30S亚基平台结构域的长距离移动，破坏了亚基间的B2b、B2c、B4、B7a和B7b桥。我们的研究结果揭示了HflXr独特的核糖体循环利用策略，该策略不同于由核糖体释放因子（RRF）和延伸因子G（EF-G）介导的策略。HflXr与管家HflX之间的相似性表明，此处报道的替代性核糖体循环利用机制在原核生物界是普遍存在的。
