9UX0

Crystal structure of the virulence effector VepA in complex with its secretion chaperone VecA

9UX0 の概要

• エントリーDOI: 10.2210/pdb9ux0/pdb
• 分子名称: Cation transporter, CesT family type III secretion system chaperone (2 entities in total)
• 機能のキーワード: vibrio parahaemolyticus, type 3 secretion system, effector, toxin
• 由来する生物種: Vibrio parahaemolyticus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 88264.08

構造登録者

Iimori, M.,Oki, H.,Akeda, Y.,Ishii, E.,Kodama, T.,Ueda, T.,Nakamura, S.,Matsuda, S.,Kawahara, K.,Iida, T. (登録日: 2025-05-13, 公開日: 2025-06-25, 最終更新日: 2025-07-02)

主引用文献

Iimori, M.,Oki, H.,Akeda, Y.,Ishii, E.,Kodama, T.,Ueda, T.,Nakamura, S.,Matsuda, S.,Kawahara, K.,Iida, T.
Structural basis of effector recognition by the T3SS chaperone VecA from Vibrio parahaemolyticus.
Biochem.Biophys.Res.Commun., 776:152190-152190, 2025

PubMed Abstract: Many pathogenic gram-negative bacteria utilise the type III secretion system (T3SS), a specific protein injection apparatus, to translocate virulence effectors into host cells, modulating host cell functions and establishing infection. To facilitate the precise cytosolic transport of effectors to T3SS, a class of proteins called chaperones plays a crucial role. However, a limited number of available structural data on chaperone-effector complexes hampers understanding of the mechanisms underlying this process. In Vibrio parahaemolyticus, a major causative agent of seafood-associated acute gastroenteritis in humans, T3SS chaperone VecA transports its cognate membrane-disrupting effector, VepA. Here, we determined the crystal structure of VecA alone and in complex with VepA at resolutions of 2.20 Å and 2.49 Å, respectively. While the overall protein fold and the hydrophobic cleft that accommodates an N-terminal β-motif of effectors were conserved among T3SS chaperones, the structural analysis revealed that surface residues are remarkably different, reflecting their substrate specificity. Additionally, unlike other reported structures of the T3SS chaperone-effector complexes, in which the effectors are partially unfolded and wrapped around the chaperone, VepA adopts a highly folded conformation in the complex. This compact structure appears to protect the fragile glycine-rich transmembrane domain of VepA and suggests that upon secretion, VepA undergoes conformational changes, including α-helix formation, allowing the transmembrane domain to embed into and disrupt the membrane of organelles containing its binding target, V-ATPase. These findings elucidate the chaperone-mediated regulation of effector transport and function of the bacterial virulence-related T3SS.

PubMed: 40517674
DOI: 10.1016/j.bbrc.2025.152190

実験手法

X-RAY DIFFRACTION (2.49 Å)