8B4A

Nativ complex of PqsE and RhlR with autoinducer C4-HSL

8B4A の概要

• エントリーDOI: 10.2210/pdb8b4a/pdb
• 関連するPDBエントリー: 7R3E 7R3J
• 分子名称: 2-aminobenzoylacetyl-CoA thioesterase, Regulatory protein RhlR, FE (III) ION, ... (5 entities in total)
• 機能のキーワード: quorum sensing, luxr-type transcriptional regulator, pseudomonas, dna binding protein, gene regulation, c4-hsl, rhamnolipid, pqs, transcription, signaling protein
• 由来する生物種: Pseudomonas aeruginosa PAO1; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 128646.05

構造登録者

Borgert, S.R.,Blankenfeldt, W. (登録日: 2022-09-20, 公開日: 2022-12-14, 最終更新日: 2024-06-19)

主引用文献

Borgert, S.R.,Henke, S.,Witzgall, F.,Schmelz, S.,Zur Lage, S.,Hotop, S.K.,Stephen, S.,Lubken, D.,Kruger, J.,Gomez, N.O.,van Ham, M.,Jansch, L.,Kalesse, M.,Pich, A.,Bronstrup, M.,Haussler, S.,Blankenfeldt, W.
Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.
Nat Commun, 13:7402-7402, 2022

PubMed Abstract: Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals.

PubMed: 36456567
DOI: 10.1038/s41467-022-35030-w

実験手法

X-RAY DIFFRACTION (3.06 Å)