PXD047927

PXD047927 is an original dataset announced via ProteomeXchange.

Title	Invasion strategy of pathogenic bacteria is reinforced by a MARTX toxin effector duet
Description	Multiple bacterial genera take advantage of the multifunctional utoprocessing repeats-in-toxin (MARTX) toxin to invade host cells1. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis2-5, is a major driver of infection6,7; however, it is not clear how the toxin induces septicemia. 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.
HostingRepository	PRIDE
AnnounceDate	2024-07-05
AnnouncementXML	Submission_2024-07-05_03:21:26.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ga Seul Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-18 22:00:09	ID requested
⏵ 1	2024-07-05 03:21:26	announced

Dataset with its publication pending

submitter keyword: MARTX toxin

Myung Hee Kim
contact affiliation	Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea
contact email	mhk8n@kribb.re.kr
lab head
Ga Seul Lee
contact affiliation	Korea Research Institute of Bioscience & Biotechnology (KRIBB)
contact email	rktmf1013@kribb.re.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047927
     1. Label: PRIDE project
     2. Name: Invasion strategy of pathogenic bacteria is reinforced by a MARTX toxin effector duet