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-Structure paper
| タイトル | Cryo-EM analysis of the Staphylococcus aureus phenol-soluble modulin exporter PmtCD apo form in detergent micelles, nanodiscs and peptidiscs. |
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| ジャーナル・号・ページ | Commun Biol, Vol. 8, Issue 1, Page 1576, Year 2025 |
| 掲載日 | 2025年11月17日 |
著者 | Jinhong Hu / Aleksander C Lazarski / Franco K K Li / Liam J Worrall / Dylan J Burgin / Natalie Zeytuni / Seth W Dickey / Michael Otto / Natalie C J Strynadka / ![]() |
| PubMed 要旨 | Staphylococci secrete amphipathic peptides known as phenol soluble modulins (PSMs) that play a variety of pathogenic roles including host cell membrane destruction, biofilm development, and the ...Staphylococci secrete amphipathic peptides known as phenol soluble modulins (PSMs) that play a variety of pathogenic roles including host cell membrane destruction, biofilm development, and the triggering of inflammatory responses. PSM export is facilitated by the essential ATP-binding cassette (ABC) transporter PmtCD, which also provides producer immunity toward the membrane-damaging PSMs. Here, we report cryo-EM structures of PmtCD in a nucleotide-free state using different membrane mimetics - detergent, nanodisc and peptidisc - all featuring the transmembrane domains in an open state with a remarkably expansive intervening lumen. The consistently sized lumen suggests the possibility for two α-helical amphipathic PSMs to pack and passage within. A continuous hydrophobic surface with no apparent single high affinity site is in keeping with the ability of PmtCD to export a variety of hydrophobic PSM peptide substrates. The ATP driven collapse of the PmtD lumen is consistent with the lateral access and extrusion mechanisms of related ABC transporters that translocate membrane embedded substrates. Along with a new ADP product complex and prior ATPγS-bound form, these structures provide insights into the export of PSMs and a foundation for design of trojan horse antimicrobials that target MRSA strains from within by blocking membranolytic PSM export. |
リンク | Commun Biol / PubMed:41249510 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.8 - 4.3 Å |
| 構造データ | EMDB-72145, PDB-9q1y: EMDB-72169, PDB-9q2n: EMDB-72172, PDB-9q2q: EMDB-72173, PDB-9q2r: |
| 化合物 | ![]() ChemComp-ADP: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / ABC transporter |
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