4K6L

Structure of Typhoid Toxin

Summary for 4K6L

• Entry DOI: 10.2210/pdb4k6l/pdb
• Descriptor: Putative pertussis-like toxin subunit, Cytolethal distending toxin subunit B homolog, GLYCEROL, ... (5 entities in total)
• Functional Keywords: complex, bacterial toxin, sugar, toxin
• Biological source: Salmonella enterica subsp. enterica serovar Typhi; More
• Cellular location: Secreted: Q8Z6A7
• Total number of polymer chains: 7
• Total formula weight: 116818.88

Authors

Gao, X.,Song, J.,Galan, J. (deposition date: 2013-04-16, release date: 2013-07-17, Last modification date: 2023-09-20)

Primary citation

Song, J.,Gao, X.,Galan, J.E.
Structure and function of the Salmonella Typhi chimaeric A(2)B(5) typhoid toxin.
Nature, 499:350-354, 2013

PubMed Abstract: Salmonella enterica serovar Typhi (S. Typhi) differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever. The molecular bases for its unique clinical presentation are unknown. Here we find that the systemic administration of typhoid toxin, a unique virulence factor of S. Typhi, reproduces many of the acute symptoms of typhoid fever in an animal model. We identify specific carbohydrate moieties on specific surface glycoproteins that serve as receptors for typhoid toxin, which explains its broad cell target specificity. We present the atomic structure of typhoid toxin, which shows an unprecedented A2B5 organization with two covalently linked A subunits non-covalently associated to a pentameric B subunit. The structure provides insight into the toxin's receptor-binding specificity and delivery mechanisms and reveals how the activities of two powerful toxins have been co-opted into a single, unique toxin that can induce many of the symptoms characteristic of typhoid fever. These findings may lead to the development of potentially life-saving therapeutics against typhoid fever.

PubMed: 23842500
DOI: 10.1038/nature12377

Experimental method

X-RAY DIFFRACTION (2.393 Å)