EMD-20640
PmtCD peptide toxin ABC exporter in nucleotide free (apo) conformation
EMD-20640
Single-particle8.14 Å
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Map released: 14/10/2020
Last modified: 14/10/2020
Sample Organism:
Staphylococcus aureus
Sample: PmtCD
Deposition Authors: Zeytuni N, Strynadka NCJ, Yu Z, Chou HT
Sample: PmtCD
Deposition Authors: Zeytuni N, Strynadka NCJ, Yu Z, Chou HT
Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins
Zeytuni N
,
Dickey SW
,
Hu J,
Chou HT
,
Worrall LJ
,
Alexander JAN
,
Carlson ML,
Nosella M,
Duong F
,
Yu Z
,
Otto M
,
Strynadka NCJ
(2020) Sci Adv , 6 , eabb8219
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(2020) Sci Adv , 6 , eabb8219
Abstract:
Staphylococcus aureus 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.
Staphylococcus aureus 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.