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Structure paper

TitleStructural insight into the ATP-driven exporter of virulent peptide toxins.
Journal, issue, pagesSci Adv, Vol. 6, Issue 40, Year 2020
Publish dateSep 30, 2020
AuthorsN 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 linksSci Adv / PubMed:32998902 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.4 - 8.14 Å
Structure data

EMDB-20640:
PmtCD peptide toxin ABC exporter in nucleotide free (apo) conformation
Method: EM (single particle) / Resolution: 8.14 Å

EMDB-22194:
PmtCD in peptidisc
Method: EM (single particle) / Resolution: 4.3 Å

22210

6xjh

EMDB-22210, PDB-6xjh:
PmtCD ABC exporter without the basket domain at C2 symmetry
Method: EM (single particle) / Resolution: 3.6 Å

22211

6xji

EMDB-22211, PDB-6xji:
PmtCD ABC exporter at C1 symmetry
Method: EM (single particle) / Resolution: 4.0 Å

PDB-6u2d:
PmtCD peptide exporter basket domain
Method: X-RAY DIFFRACTION / Resolution: 2.11 Å

PDB-6xfu:
PmtCD peptide exporter basket domain
Method: X-RAY DIFFRACTION / Resolution: 1.4 Å

Chemicals

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-IOD:
IODIDE ION / Iodide

ChemComp-HOH:
WATER / Water

ChemComp-SCN:
THIOCYANATE ION / Thiocyanate

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

Source
  • staphylococcus aureus (bacteria)
  • Staphylococcus aureus
KeywordsMEMBRANE PROTEIN / ABC transporter / ABC exporter / Peptide transort

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