A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system

• Published in: Nature structural & molecular biology Vol. 16; no. 5; pp. 468 - 476
• Main Authors: Strynadka, Natalie C J, Spreter, Thomas, Yip, Calvin K, Sanowar, Sarah, André, Ingemar, Kimbrough, Tyler G, Vuckovic, Marija, Pfuetzner, Richard A, Deng, Wanyin, Yu, Angel C, Finlay, B Brett, Baker, David, Miller, Samuel I
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-05-2009; Nature Publishing Group
• Subjects: Amino Acid Motifs; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacterial Proteins - ultrastructure; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Cellular biology; Conserved Sequence; Crystal structure; Crystallography, X-Ray; Health aspects; Life Sciences; Membrane Biology; Membrane proteins; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Membranes; Models, Molecular; Molecular biology; Pathogens; Periplasm; Periplasm - metabolism; Physiological aspects; Protein folding; Protein Structure; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Proteins; Salmonella typhimurium - pathogenicity; Secretin - chemistry; Secretin - metabolism; Structure; Structure-Activity Relationship; Virulence Factors - chemistry; Virulence Factors - metabolism; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1603

The type III secretion system (T3SS) of pathogenic bacteria is composed of a series of rings in the inner and outer bacterial membranes. Crystallographic studies of EscJ and PrgH, proteins that comprise the two inner membrane rings of the T3SS, suggest that a conserved structural motif serves as a platform for ring assembly. Additional docking and modeling studies reveal details of the T3SS architecture and assembly.
The type III secretion system (T3SS) is a macromolecular 'injectisome' that allows bacterial pathogens to transport virulence proteins into the eukaryotic host cell. This macromolecular complex is composed of connected ring-like structures that span both bacterial membranes. The crystal structures of the periplasmic domain of the outer membrane secretin EscC and the inner membrane protein PrgH reveal the conservation of a modular fold among the three proteins that form the outer membrane and inner membrane rings of the T3SS. This leads to the hypothesis that this conserved fold provides a common ring-building motif that allows for the assembly of the variably sized outer membrane and inner membrane rings characteristic of the T3SS. Using an integrated structural and experimental approach, we generated ring models for the periplasmic domain of EscC and placed them in the context of the assembled T3SS, providing evidence for direct interaction between the outer membrane and inner membrane ring components and an unprecedented span of the outer membrane secretin.