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-Structure paper
Title | Ribosome protection by antibiotic resistance ATP-binding cassette protein. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 115, Issue 20, Page 5157-5162, Year 2018 |
Publish date | May 15, 2018 |
Authors | Weixin 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 Abstract | 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 ...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 links | Proc Natl Acad Sci U S A / PubMed:29712846 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.6 Å |
Structure data | |
Chemicals | ChemComp-MG: ChemComp-ANP: |
Source |
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Keywords | RIBOSOME / Antibiotics / Macrolides / ABC-F protein / AZM |