7P48

Staphylococcus aureus ribosome in complex with Sal(B)

This is a non-PDB format compatible entry.

Summary for 7P48

• Entry DOI: 10.2210/pdb7p48/pdb
• EMDB information: 13191
• Descriptor: 50S ribosomal protein L33, 50S ribosomal protein L2, 50S ribosomal protein L3, ... (56 entities in total)
• Functional Keywords: antibiotic resistance, abc-f protein, ribosome, ribosomal protein
• Biological source: Staphylococcus lentus; More
• Total number of polymer chains: 53
• Total formula weight: 2229866.32

Authors

Nicholson, D.,Ranson, N.A.,O'Neill, A.J. (deposition date: 2021-07-09, release date: 2022-02-02, Last modification date: 2022-03-09)

Primary citation

Mohamad, M.,Nicholson, D.,Saha, C.K.,Hauryliuk, V.,Edwards, T.A.,Atkinson, G.C.,Ranson, N.A.,O'Neill, A.J.
Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci.
Nucleic Acids Res., 50:2128-2142, 2022

PubMed Abstract: The first member of the pleuromutilin (PLM) class suitable for systemic antibacterial chemotherapy in humans recently entered clinical use, underscoring the need to better understand mechanisms of PLM resistance in disease-causing bacterial genera. Of the proteins reported to mediate PLM resistance in staphylococci, the least-well studied to date is Sal(A), a putative ABC-F NTPase that-by analogy to other proteins of this type-may act to protect the ribosome from PLMs. Here, we establish the importance of Sal proteins as a common source of PLM resistance across multiple species of staphylococci. Sal(A) is revealed as but one member of a larger group of Sal-type ABC-F proteins that vary considerably in their ability to mediate resistance to PLMs and other antibiotics. We find that specific sal genes are intrinsic to particular staphylococcal species, and show that this gene family is likely ancestral to the genus Staphylococcus. Finally, we solve the cryo-EM structure of a representative Sal-type protein (Sal(B)) in complex with the staphylococcal 70S ribosome, revealing that Sal-type proteins bind into the E site to mediate target protection, likely by displacing PLMs and other antibiotics via an allosteric mechanism.

PubMed: 35137182
DOI: 10.1093/nar/gkac058

Experimental method

ELECTRON MICROSCOPY (2.9 Å)