8KA2

Crystal structure of the RID-dependent transforming NADase domain (RDTND)/calmodulin-binding domain of Rho inactivation domain (RID-CBD) from Vibrio vulnificus

8KA2 の概要

• エントリーDOI: 10.2210/pdb8ka2/pdb
• 分子名称: RDTND-RID CBD (1 entity in total)
• 機能のキーワード: martx toxin, rdtnd-rid, nadase, toxin
• 由来する生物種: Vibrio vulnificus (DUF1-RIDcbd)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95267.67

構造登録者

Lee, Y.,Choi, S.,Hwang, J.,Kim, M.H. (登録日: 2023-08-02, 公開日: 2024-07-10, 最終更新日: 2024-11-13)

主引用文献

Choi, S.,Lee, Y.,Park, S.,Jang, S.Y.,Park, J.,Oh, D.W.,Kim, S.M.,Kim, T.H.,Lee, G.S.,Cho, C.,Kim, B.S.,Lee, D.,Kim, E.H.,Cheong, H.K.,Moon, J.H.,Song, J.J.,Hwang, J.,Kim, M.H.
Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet.
Nat Commun, 15:6218-6218, 2024

PubMed Abstract: Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P) and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

PubMed: 39043696
DOI: 10.1038/s41467-024-50650-0

実験手法

X-RAY DIFFRACTION (3.38 Å)