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-Structure paper
タイトル | Structural basis of peptide secretion for Quorum sensing by ComA. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 7178, Year 2023 |
掲載日 | 2023年11月7日 |
著者 | Lin Yu / Xin Xu / Wan-Zhen Chua / Hao Feng / Zheng Ser / Kai Shao / Jian Shi / Yumei Wang / Zongli Li / Radoslaw M Sobota / Lok-To Sham / Min Luo / |
PubMed 要旨 | Quorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as ...Quorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as Streptococcus pneumoniae, ComA is a conserved efflux pump responsible for the maturation and secretion of peptide signals, including the competence-stimulating peptide (CSP), yet its structure and function remain unclear. Here, we functionally characterize ComA as an ABC transporter with high ATP affinity and determined its cryo-EM structures in the presence or absence of CSP or nucleotides. Our findings reveal a network of strong electrostatic interactions unique to ComA at the intracellular gate, a putative binding pocket for two CSP molecules, and negatively charged residues facilitating CSP translocation. Mutations of these residues affect ComA's peptidase activity in-vitro and prevent CSP export in-vivo. We demonstrate that ATP-Mg triggers the outward-facing conformation of ComA for CSP release, rather than ATP alone. Our study provides molecular insights into the QS signal peptide secretion, highlighting potential targets for QS-targeting drugs. |
リンク | Nat Commun / PubMed:37935699 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 8.2 Å |
構造データ | EMDB-34712, PDB-8hf4: EMDB-34713, PDB-8hf5: EMDB-34714, PDB-8hf6: EMDB-34715, PDB-8hf7: EMDB-34716: Cryo-EM structure of ComC bound ComA C17A at inward-facing state EMDB-36882, PDB-8k4b: EMDB-36936, PDB-8k7a: |
化合物 | ChemComp-AGS: ChemComp-MG: ChemComp-ATP: ChemComp-ZN: |
由来 |
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キーワード | MEMBRANE PROTEIN / TRANSPORT PROTEIN / ABC transport / PCAT / HYDROLASE / TRANSLOCASE / ABC transporter |