8TED

PorX primitive orthorhombic crystal form

8TED の概要

• エントリーDOI: 10.2210/pdb8ted/pdb
• 分子名称: Response regulator receiver protein, BROMIDE ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: type-ix secretion system, response regulator, alkaline phosphatase, signaling protein
• 由来する生物種: Flavobacterium johnsoniae UW101
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123181.83

構造登録者

Saran, A.,Zeytuni, N. (登録日: 2023-07-06, 公開日: 2024-04-17, 最終更新日: 2024-10-30)

主引用文献

Saran, A.,Kim, H.M.,Manning, I.,Hancock, M.A.,Schmitz, C.,Madej, M.,Potempa, J.,Sola, M.,Trempe, J.F.,Zhu, Y.,Davey, M.E.,Zeytuni, N.
Unveiling the molecular mechanisms of the type IX secretion system's response regulator: Structural and functional insights.
Pnas Nexus, 3:pgae316-pgae316, 2024

PubMed Abstract: The type IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both and . First, our structural studies revealed PorX harbors a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX's effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX's dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in and affects metabolic enzymes secretion in the nonpathogenic , but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.

PubMed: 39139265
DOI: 10.1093/pnasnexus/pgae316

実験手法

X-RAY DIFFRACTION (2.1 Å)