9HT3

Crystal structure of PA0884, the SBP component of a Pseudomonas aeruginosa PAO1 Tripartite ATP-independent Periplasmic (TRAP) transporter, complexed with itaconate

9HT3 の概要

• エントリーDOI: 10.2210/pdb9ht3/pdb
• 分子名称: Probable C4-dicarboxylate-binding periplasmic protein, 2-methylidenebutanedioic acid, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: periplasmic substrate binding protein, c4-dicarboxylate transport, itaconate, transport protein
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70377.55

構造登録者

Herman, R.,Mehboob, J.,Elston, R.,Afolabi, H.,Kinniment-Williams, B.E.,Wilkinson, A.J.,Thomas, G.H. (登録日: 2024-12-19, 公開日: 2025-09-10, 最終更新日: 2025-11-19)

主引用文献

Mehboob, J.,Herman, R.,Elston, R.C.,Afolabi, H.,Kinniment-Williams, B.E.,van der Woude, M.W.,Wilkinson, A.J.,Thomas, G.H.
Itaconate utilisation by the human pathogen Pseudomonas aeruginosa requires uptake via the IctPQM TRAP transporter.
Biochem.J., 482:1277-1288, 2025

PubMed Abstract: Pseudomonas aeruginosa PA01 is one of the major causes of disease persistence and mortality in patients with lung pathologies, relying on various host metabolites as carbon and energy sources for growth. The ict-ich-ccl operon (pa0878, pa0882 and pa0883) in PAO1 is required for growth on the host molecule itaconate, a C5-dicarboxylate. However, it is not known how itaconate is taken up into P. aeruginosa. Here, we demonstrate that a genetically linked tripartite ATP-independent periplasmic (TRAP) transporter (pa0884-pa0886), which is homologous to the known C4-dicarboxylate-binding TRAP system, is essential for growth on itaconate, but not for the closely related C4-dicarboxylate succinate. Using tryptophan fluorescence spectroscopy, we demonstrate that the substrate-binding protein (SBP), IctP (PA0884), binds itaconate but still retains higher affinity for the related C4-dicarboxylates. The structures of IctP bound to itaconate (1.80 Å) and succinate (1.75 Å) revealed an enclosed ligand-binding pocket with ion pairing interactions with the ligand carboxylates. The C2 methylene group that is the distinguishing feature of itaconate compared with succinate is accommodated by a unique change in the IctP-binding site from a Leu to Val, which distinguishes it from closely related C4-dicarboxylate-binding SBPs. Together, these data suggest that this transporter, which we name IctPQM, has duplicated from a canonical C4-dicarboxylate transporter, and its evolution towards itaconate specificity enables this pathogen to now access a key metabolite for persistence in the host.

PubMed: 40891131
DOI: 10.1042/BCJ20253132

実験手法

X-RAY DIFFRACTION (1.8 Å)