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Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins

N Zeytuni1, S W Dickey2, J Hu1

  • 1Department of Biochemistry and Molecular Biology and the Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.

Science Advances
|October 1, 2020
PubMed

Insights

Researchers identified the minimal protein unit, PmtCD, essential for exporting Staphylococcus aureus toxins (PSMs). Structural analysis reveals its mechanism, aiding in developing new therapies against antibiotic-resistant bacteria.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • Staphylococcus aureus is a significant human pathogen with increasing antibiotic resistance.
  • Phenol-soluble modulins (PSMs) are key toxins secreted by S. aureus, contributing to infection.
  • PSM export relies on the adenosine 5 -triphosphate (ATP)-binding cassette (ABC) transporter complex, PmtABCD.

Purpose of the Study:

  • To determine the minimal functional unit of the PSM transporter complex.
  • To elucidate the atomic structure of the PSM transporter.
  • To understand the mechanism of PSM peptide export.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) at near-atomic resolution.
  • X-ray crystallography.
  • Biochemical assays to characterize transporter function.

Main Results:

  • The minimal PSM exporter unit was identified as PmtCD.
  • The atomic structure of PmtCD in an ATP-bound state was determined, revealing a type II ABC exporter fold with an additional cytosolic domain.
  • A nucleotide-free conformation showed an open state with a hydrophobic chamber potentially binding two PSM peptides.

Conclusions:

  • PmtCD is the essential unit for PSM export.
  • The determined structures provide mechanistic insights into PSM transport.
  • This structural information can guide the development of novel therapeutics against S. aureus infections.

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