Year: 2023
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: U.S. Department of Health and Human Services, Simons Foundation, Yale University, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: National Resource for Automated Molecular Microscopy, Systematic Discovery and Analysis of Small Proteins and Small ORFs in Mycobacteria, G1926414987, G2589371465, An Ultra-Performance Liquid Chromatography System to Support Metabolomics at Yale University, G312200990, Role of ribosome modulating proteins in conferring Mycobacterium abscessus antibiotic resistance, G4931614974, High Resolution Tandem Mass Spectrometer to Meet Growing Demand for Proteomics at Yale, G5520316217, Structural Aspects of Protein Synthesis in the Mammalian Mitochondria, 6500 QTrap Mass Spectrometer for Yale University, Alternative Ribosomes & Antibiotic Tolerance in Mycobacteria, G966245560
OpenAlex ID: W4388040938