Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition.,Nature Communications

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Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition.
Nature Communications ( IF 14.7 ) Pub Date : 2019-10-08 , DOI: 10.1038/s41467-019-12589-5
Dmitrii Y Travin _{1,

2} , Zoe L Watson ₃ , Mikhail Metelev _{1,

2,

4} , Fred R Ward ₅ , Ilya A Osterman _{1,

6} , Irina M Khven _{6,

7} , Nelli F Khabibullina _{8,

9} , Marina Serebryakova ₁₀ , Peter Mergaert ₁₁ , Yury S Polikanov _{8,

12} , Jamie H D Cate _{3,

5} , Konstantin Severinov _{1,

2,

13}

Affiliation

Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia.
Institute of Gene Biology, Russian Academy of Science, Moscow, Russia.
Department of Chemistry, University of California, Berkeley, USA.
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA.
National Medical Research Center for Phthisiopulmology & Infectious Diseases, Moscow, Russia.
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Institute for Integrative Biology of the Cell (I2BC), CNRS CEA University Paris-Sud, University Paris-Saclay, Gif-sur-Yvette, France.
Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, USA.
Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, USA.

Ribosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) - an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants. The cryo-EM structure of the Escherichia coli 70S-PHZ complex reveals that the drug interacts with the 23S rRNA and uL4/uL22 proteins and obstructs ribosomal exit tunnel in a way that is distinct from other compounds. We show that the uL4 loop sequence determines the species-specificity of antibiotic action. PHZ expands the known diversity of LAPs and may be used in the future as biocontrol agent for agricultural needs.

中文翻译：

核糖体结合的唑修饰的肽phazolicin的结构使其细菌翻译抑制的物种特异性模式合理化。

核糖体合成的翻译后修饰肽（RiPPs）代表了具有各种生物活性的天然产物的快速扩展类别。线性的含氮杂（in）e的肽（LAP）包含RiPPs的一个子类，该子类显示出出色的作用机理多样性，同时具有共同的结构特征。在这里，我们报告在根瘤菌Pop5基因组中发现一个新的LAP生物合成基因簇，该簇编码前体肽和phazolicin（PHZ）的修饰机制-广泛修饰的肽对豆类的一些共生细菌表现出窄谱抗菌活性植物。大肠杆菌70S-PHZ复合物的冷冻EM结构表明，该药物与23S rRNA和uL4 / uL22蛋白相互作用，并以不同于其他化合物的方式阻塞了核糖体出口通道。我们表明，uL4环序列决定了抗生素作用的物种特异性。PHZ扩大了LAP的已知多样性，将来可以用作农业需求的生物防治剂。

更新日期：2019-10-08

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