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

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Science Advances. 2020 Sep 30;6(40). doi: 10.1126/sciadv.abb8219

Structural insight into the ATP-driven exporter of virulent peptide toxins. Cryo-Electron Microscopy

Zeytuni N, Dickey SW, Hu J, Chou HT, Worrall LJ, Alexander JA, Carlson ML, Nosella M, Duong F, Yu Z, Otto M, Strynadka NC

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Abstract

is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an "open" conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.

PMID: 32998902 [PubMed - indexed for MEDLINE]

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

Abstract

PMID: 32998902 [PubMed - indexed for MEDLINE]

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