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-Structure paper
Title | Structural insight into the ATP-driven exporter of virulent peptide toxins. |
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Journal, issue, pages | Sci Adv, Vol. 6, Issue 40, Year 2020 |
Publish date | Sep 30, 2020 |
Authors | N Zeytuni / S W Dickey / J Hu / H T Chou / L J Worrall / J A N Alexander / M L Carlson / M Nosella / F Duong / Z Yu / M Otto / N C J Strynadka / |
PubMed 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 ... 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. |
External links | Sci Adv / PubMed:32998902 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.4 - 8.14 Å |
Structure data | EMDB-20640: EMDB-22194: EMDB-22210, PDB-6xjh: EMDB-22211, PDB-6xji: PDB-6u2d: PDB-6xfu: |
Chemicals | ChemComp-SO4: ChemComp-IOD: ChemComp-HOH: ChemComp-SCN: ChemComp-AGS: ChemComp-MG: |
Source |
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Keywords | MEMBRANE PROTEIN / ABC transporter / ABC exporter / Peptide transort |