Abstract
The T3SS injectisome is a syringe-shaped macromolecular assembly found in pathogenic Gram-negative bacteria that allows for the direct delivery of virulence effectors into host cells. It is composed of a “basal body”, a lock-nut structure spanning both bacterial membranes, and a “needle” that protrudes away from the bacterial surface. A hollow channel spans throughout the apparatus, permitting the translocation of effector proteins from the bacterial cytosol to the host plasma membrane. The basal body is composed largely of three membrane-embedded proteins that form oligomerized concentric rings. Here, we report the crystal structures of three domains of the prototypical Salmonella SPI-1 basal body, and use a new approach incorporating symmetric flexible backbone docking and EM data to produce a model for their oligomeric assembly. The obtained models, validated by biochemical and in vivo assays, reveal the molecular details of the interactions driving basal body assembly, and notably demonstrate a conserved oligomerization mechanism.
Highlights
The bacterial injectisome, or type III secretion system (T3SS), is a specialized syringe-shaped protein-export system utilized by many pathogenic Gram-negative bacteria for the injection of virulence proteins into host cells
The major structural scaffold of the basal body is comprised largely of three proteins that arrange into a series of highly oligomerized, concentric rings: two intimately associated proteins localized to the IM - PrgK/EscJ/MxiJ and PrgH/EscD/MxiG, and a third protein belonging to the secretin family of OM proteins, InvG/EscC/MxiD (Salmonella enterica serovar Typhimurium Salmonella Pathogenicity Islands (SPI)-1, Enteropathogenic Escherichia coli (EPEC) LEE and Shigella dysenteriae nomenclature, respectively) (Figure 1A) [4,5,6,7,8]
Two of the major virulence determining factors are the discrete T3SSs encoded by the Salmonella Pathogenicity Islands (SPI) 1 and 2, which are required for bacterial invasion and replication within host cells [9]
Summary
The bacterial injectisome, or type III secretion system (T3SS), is a specialized syringe-shaped protein-export system utilized by many pathogenic Gram-negative bacteria for the injection of virulence proteins (effectors) into host cells. The major structural scaffold of the basal body is comprised largely of three proteins that arrange into a series of highly oligomerized, concentric rings: two intimately associated proteins localized to the IM - PrgK/EscJ/MxiJ and PrgH/EscD/MxiG, and a third protein belonging to the secretin family of OM proteins, InvG/EscC/MxiD (Salmonella enterica serovar Typhimurium SPI-1, Enteropathogenic Escherichia coli (EPEC) LEE and Shigella dysenteriae nomenclature, respectively) (Figure 1A) [4,5,6,7,8]. The SPI-1 system, belonging to the mxi-spa evolutionary family which includes the Shigella dysenteriae T3SS [10], is considered the prototypical T3SS and has been the focus of structural characterization using a variety of techniques including the first cryoelectron microscopy (EM) 3D reconstruction of a T3SS needle
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