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TitleRibosome protection by antibiotic resistance ATP-binding cassette protein.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 20, Page 5157-5162, Year 2018
Publish dateMay 15, 2018
AuthorsWeixin Su / Veerendra Kumar / Yichen Ding / Rya Ero / Aida Serra / Benjamin Sian Teck Lee / Andrew See Weng Wong / Jian Shi / Siu Kwan Sze / Liang Yang / Yong-Gui Gao /
PubMed AbstractThe ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer ...The ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer resistance to ribosome-targeting antibiotics through a yet unknown mechanism. Among them, MsrE has been implicated in macrolide resistance. Here, we report the cryo-EM structure of ATP form MsrE bound to the ribosome. Unlike previously characterized ribosomal protection proteins, MsrE is shown to bind to ribosomal exit site. Our structure reveals that the domain linker forms a unique needle-like arrangement with two crossed helices connected by an extended loop projecting into the peptidyl-transferase center and the nascent peptide exit tunnel, where numerous antibiotics bind. In combination with biochemical assays, our structure provides insight into how MsrE binding leads to conformational changes, which results in the release of the drug. This mechanism appears to be universal for the ABC-F type ribosome protection proteins.
External linksProc Natl Acad Sci U S A / PubMed:29712846 / PubMed Central
MethodsEM (single particle)
Resolution3.6 Å
Structure data

6934

5zlu

EMDB-6934, PDB-5zlu:
Ribosome Structure bound to ABC-F protein.
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • Thermus thermophilus (bacteria)
  • thermus thermophilus hb8 (bacteria)
  • thermus thermophilus (strain hb8 / atcc 27634 / dsm 579) (bacteria)
  • pseudomonas aeruginosa (bacteria)
KeywordsRIBOSOME / Antibiotics / Macrolides / ABC-F protein / AZM

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