A Refined Model of the Prototypical Salmonella SPI-1 T3SS Basal Body Reveals the Molecular Basis for Its Assembly

PLoS Pathogens

Marija Vuckovic¹  Angel C. Yu¹  Julien R. C. Bergeron¹  Liam J. Worrall¹  Nikolaos G. Sgourakis²  Frank DiMaio²  David Baker³  Natalie C. J. Strynadka⁴  Heather B. Felise⁵  Richard A. Pfuetzner⁵  Samuel I. Miller⁵ 

[1] Department of Biochemistry and Molecular Biology, and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada;Department of Biochemistry, University of Washington, Seattle, Washington, United States of America;Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America;Department of Medicine, University of Washington, Seattle, Washington, United States of America;Department of Microbiology, University of Washington, Seattle, Washington, United States of America

关键词: Crystal structure;    Secretion;    Salmonella typhimurium;    Secretin;    Crystals;    Protein structure;    Salmonella;    Shigella;   

DOI  :  10.1371/journal.ppat.1003307

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY