Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
University of California at Berkeley, Berkeley, CA, USA.
Nat Commun. 2023 Oct 31;14(1):6961. doi: 10.1038/s41467-023-42266-7.
The spirochete bacterial pathogen Borrelia (Borreliella) burgdorferi (Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target the Bbu ribosome. Here we present the structure of the Bbu 70S ribosome obtained by single particle cryo-electron microscopy at 2.9 Å resolution, revealing a bound hibernation promotion factor protein and two genetically non-annotated ribosomal proteins bS22 and bL38. The ribosomal protein uL30 in Bbu has an N-terminal α-helical extension, partly resembling the mycobacterial bL37 protein, suggesting evolution of bL37 and a shorter uL30 from a longer uL30 protein. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energy predictions for antibiotics reflect subtle distinctions in antibiotic-binding sites in the Bbu ribosome. Discovery of these features in the Bbu ribosome may enable better ribosome-targeted antibiotic design for Lyme disease treatment.
螺旋体细菌病原体伯氏疏螺旋体（Borreliella）burgdorferi（Bbu）影响全球超过 10%的人口，并且每年在美国导致约 50 万人患有莱姆病。莱姆病的治疗包括针对 Bbu 核糖体的抗生素。在这里，我们通过单颗粒冷冻电镜在 2.9 Å 的分辨率下获得了 Bbu 70S 核糖体的结构，揭示了一个结合的休眠促进因子蛋白和两个遗传上未注释的核糖体蛋白 bS22 和 bL38。Bbu 中的核糖体蛋白 uL30 具有 N 端α-螺旋延伸，部分类似于分枝杆菌 bL37 蛋白，表明 bL37 和较短的 uL30 是从较长的 uL30 蛋白进化而来的。它与哺乳动物线粒体核糖体中的蛋白质 uL30m 和 mL63 的类似性也表明了哺乳动物线粒体核糖体中蛋白质含量扩展的可能进化途径。抗生素的计算结合自由能预测反映了 Bbu 核糖体中抗生素结合位点的细微差异。在 Bbu 核糖体中发现这些特征可能能够更好地针对核糖体设计用于治疗莱姆病的抗生素。
