title: A central interdomain protein joint in elongation factor G regulates antibiotic sensitivity, GTP hydrolysis, and ribosome translocation.
abstract: The antibiotic fusidic acid potently inhibits bacterial translation (and cellular growth) by lodging between domains I and III of elongation factor G (EF-G) and preventing release of EF-G from the ribosome. We examined the functions of key amino acid residues near the active site of EF-G that interact with fusidic acid and regulate hydrolysis of GTP. Alanine mutants of these residues spontaneously hydrolyzed GTP in solution, bypassing the normal activating role of the ribosome. A conserved phenylalanine in the switch II element of EF-G was important for suppressing GTP hydrolysis in solution and critical for catalyzing translocation of the ribosome along mRNA. These experimental results reveal the multipurpose roles of an interdomain joint in the heart of an essential translation factor that can both promote and inhibit bacterial translation.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ticu
authors.forename: Marat
authors.initials: M
authors.lastname: Murataliev
authors.forename: Roxana
authors.initials: R
authors.lastname: Nechifor
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Wilson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020134:Catalytic Domain; D004926:Escherichia coli / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry*; D006868:Hydrolysis; D008954:Models, Biological; D008968:Molecular Conformation; D009154:Mutation; D020653:Peptide Elongation Factor G / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry*; D014178:Translocation, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D020653:Peptide Elongation Factor G; D012333:RNA, Messenger; D010649:Phenylalanine; D006160:Guanosine Triphosphate