Characterisation of a tripartite α-pore forming toxin from Serratia marcescens

• Published in: Scientific reports Vol. 11; no. 1; p. 6447
• Main Authors: Churchill-Angus, Alicia M., Schofield, Thomas H. B., Marlow, Thomas R., Sedelnikova, Svetlana E., Wilson, Jason S., Rafferty, John B., Baker, Patrick J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-03-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/326/41; 631/326/41/1319; 631/45; 631/45/535; 631/45/612; 631/45/612/1237; 631/535; Antibiotics; Bacteria; ClyA protein; Efficiency; Gram-negative bacteria; Humanities and Social Sciences; Infections; Molecular biology; multidisciplinary; Pore-forming proteins; Proteins; Science; Science (multidisciplinary); Sequence analysis; Serratia marcescens; Toxins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85726-0

Tripartite members of the ClyA family of α-PFTs have recently been identified in a number of pathogenic Gram-negative bacteria, including the human pathogen
Serratia marcescens
. Structures of a Gram-negative A component and a tripartite α-PFT complete pore are unknown and a mechanism for pore formation is still uncertain. Here we characterise the tripartite SmhABC toxin from
S. marcescens
and propose a mechanism of pore assembly. We present the structure of soluble SmhA, as well as the soluble and pore forms of SmhB. We show that the β-tongue soluble structure is well conserved in the family and propose two conserved latches between the head and tail domains that are broken on the soluble to pore conformational change. Using the structures of individual components, sequence analysis and docking predictions we illustrate how the A, B and C protomers would assemble on the membrane to produce a complete tripartite α-PFT pore.