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

DOI: 10.1038/s41598-021-85726-0 DOI Help

Authors: Alicia M. Churchill-Angus (University of Sheffield) , Thomas Schofield (University of Sheffield; University of Leeds) , Thomas R. Marlow (University of Sheffield) , Svetlana E. Sedelnikova (University of Sheffield) , Jason S. Wilson (University of Sheffield) , John B. Rafferty (University of Sheffield) , Patrick J. Baker (University of Sheffield)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 11

State: Published (Approved)
Published: March 2021
Diamond Proposal Number(s): 17773 , 24447

Open Access Open Access

Abstract: 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.

Journal Keywords: Bacteria; Bacterial toxins; Biochemistry; Membrane proteins; Microbiology; Proteins; Structural biology

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I24-Microfocus Macromolecular Crystallography


Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Antibiotic Resistance Infectious Diseases Pathogens Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)