6HA8

Cryo-EM structure of the ABCF protein VmlR bound to the Bacillus subtilis ribosome

This is a non-PDB format compatible entry.

Summary for 6HA8

• Entry DOI: 10.2210/pdb6ha8/pdb
• Related: 6HA1
• EMDB information: 0176 0177
• Descriptor: 23S rRNA, 50S ribosomal protein L15, 50S ribosomal protein L16, ... (55 entities in total)
• Functional Keywords: single particle cryo-em, abcf, atpase, ribosome, antibiotic resistiance
• Biological source: Bacillus subtilis (strain 168); More
• Total number of polymer chains: 53
• Total formula weight: 2219810.37

Authors

Crowe-McAuliffe, C.,Graf, M.,Huter, P.,Abdelshahid, M.,Novacek, J.,Wilson, D.N. (deposition date: 2018-08-07, release date: 2018-08-29, Last modification date: 2021-01-27)

Primary citation

Crowe-McAuliffe, C.,Graf, M.,Huter, P.,Takada, H.,Abdelshahid, M.,Novacek, J.,Murina, V.,Atkinson, G.C.,Hauryliuk, V.,Wilson, D.N.
Structural basis for antibiotic resistance mediated by theBacillus subtilisABCF ATPase VmlR.
Proc. Natl. Acad. Sci. U.S.A., 115:8978-8983, 2018

PubMed Abstract: Many Gram-positive pathogenic bacteria employ ribosomal protection proteins (RPPs) to confer resistance to clinically important antibiotics. In , the RPP VmlR confers resistance to lincomycin (Lnc) and the streptogramin A (S) antibiotic virginiamycin M (VgM). VmlR is an ATP-binding cassette (ABC) protein of the F type, which, like other antibiotic resistance (ARE) ABCF proteins, is thought to bind to antibiotic-stalled ribosomes and promote dissociation of the drug from its binding site. To investigate the molecular mechanism by which VmlR confers antibiotic resistance, we have determined a cryo-electron microscopy (cryo-EM) structure of an ATPase-deficient VmlR-EQ mutant in complex with a ErmDL-stalled ribosomal complex (SRC). The structure reveals that VmlR binds within the E site of the ribosome, with the antibiotic resistance domain (ARD) reaching into the peptidyltransferase center (PTC) of the ribosome and a C-terminal extension (CTE) making contact with the small subunit (SSU). To access the PTC, VmlR induces a conformational change in the P-site tRNA, shifting the acceptor arm out of the PTC and relocating the CCA end of the P-site tRNA toward the A site. Together with microbiological analyses, our study indicates that VmlR allosterically dissociates the drug from its ribosomal binding site and exhibits specificity to dislodge VgM, Lnc, and the pleuromutilin tiamulin (Tia), but not chloramphenicol (Cam), linezolid (Lnz), nor the macrolide erythromycin (Ery).

PubMed: 30126986
DOI: 10.1073/pnas.1808535115

Experimental method

ELECTRON MICROSCOPY (3.5 Å)