8HF6

Cryo-EM structure of nucleotide-bound ComA E647Q mutant

8HF6 の概要

• エントリーDOI: 10.2210/pdb8hf6/pdb
• EMDBエントリー: 34712 34713 34714 34715 34716
• 分子名称: Competence factor transporting ATP-binding protein/permease ComA, ADENOSINE-5'-TRIPHOSPHATE (2 entities in total)
• 機能のキーワード: abc transporter, pcat, membrane protein, transport protein, hydrolase, translocase
• 由来する生物種: Streptococcus pneumoniae D39
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 161878.44

構造登録者

Yu, L.,Xin, X.,Min, L. (登録日: 2022-11-09, 公開日: 2023-10-04, 最終更新日: 2024-03-06)

主引用文献

Yu, L.,Xu, X.,Chua, W.Z.,Feng, H.,Ser, Z.,Shao, K.,Shi, J.,Wang, Y.,Li, Z.,Sobota, R.M.,Sham, L.T.,Luo, M.
Structural basis of peptide secretion for Quorum sensing by ComA.
Nat Commun, 14:7178-7178, 2023

PubMed Abstract: 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.

PubMed: 37935699
DOI: 10.1038/s41467-023-42852-9

実験手法

ELECTRON MICROSCOPY (3.1 Å)