RRC ID 53689
著者 Seefeldt AC, Nguyen F, Antunes S, Pérébaskine N, Graf M, Arenz S, Inampudi KK, Douat C, Guichard G, Wilson DN, Innis CA.
タイトル The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking and destabilizing the initiation complex.
ジャーナル Nat Struct Mol Biol
Abstract The increasing prevalence of multidrug-resistant pathogenic bacteria is making current antibiotics obsolete. Proline-rich antimicrobial peptides (PrAMPs) display potent activity against Gram-negative bacteria and thus represent an avenue for antibiotic development. PrAMPs from the oncocin family interact with the ribosome to inhibit translation, but their mode of action has remained unclear. Here we have determined a structure of the Onc112 peptide in complex with the Thermus thermophilus 70S ribosome at a resolution of 3.1 Å by X-ray crystallography. The Onc112 peptide binds within the ribosomal exit tunnel and extends toward the peptidyl transferase center, where it overlaps with the binding site for an aminoacyl-tRNA. We show biochemically that the binding of Onc112 blocks and destabilizes the initiation complex, thus preventing entry into the elongation phase. Our findings provide a basis for the future development of this class of potent antimicrobial agents.
巻・号 22(6)
ページ 470-5
公開日 2015-6-1
DOI 10.1038/nsmb.3034
PII nsmb.3034
PMID 25984971
MeSH Antimicrobial Cationic Peptides / metabolism Antimicrobial Cationic Peptides / pharmacology* Crystallography, X-Ray Models, Molecular Peptide Chain Initiation, Translational / drug effects* Protein Conformation Protein Synthesis Inhibitors / metabolism Protein Synthesis Inhibitors / pharmacology* Ribosomes / chemistry* Ribosomes / metabolism Thermus thermophilus / chemistry Thermus thermophilus / drug effects
IF 11.98
引用数 75
リソース情報
原核生物(大腸菌)