Type III secretion systems shape up as they ship out

Abstract

Virulence associated protein type III secretion systems (T3SSs) are intricately structured organic nanosyringes that achieve the translocation of bacterial proteins from the prokaryotic cytoplasm across three membranes into the host cytosol. The substrates for these systems number in the hundreds, with remarkably diverse biological activities, modulating host cell biology for the benefit of the pathogen. Although there has been tremendous progress on the structure and function of the T3SS substrates, there has been comparatively little progress on the much more highly conserved secretion apparatus itself. This review summarizes recent advances in the field of structural microbiology that have begun to address this shortcoming, finally bringing to bear the power of structural biology to this central virulence system of Gram-negative bacterial pathogens.

Figure 1. An Organic Nanosyringe

A schematic representation of the protein Type III Secretion System (T3SS) of Salmonella focusing on the basal body of the nanomachine. The inner and outer membranes of the bacterium are shown along with the peptidoglycan layer. The three proteins of the basal body (PrgH, PrgK, and InvG from the Salmonella SPI-1 pathogenicity island) are labeled, and drawn to roughly correspond the EM reconstructions and biochemical experiments localizing the polypeptides. The needle filament (PrgI) is also depicted, as are the tip protein (SipD) and the translocon pore (SipB/SipC) in the eukaryotic plasma membrane. Approximate dimensions for the apparatus are also shown.

Figure 2. Architecture of needle complexes from Shigella and Salmonella

Cut-away view of side views of the base and the needle complexes from Shigella (EmDep accession number EMD-1617) and Salmonella obtained from cryo-electron microscopy images and single particle reconstructions (EmDep accession numbers 1100, 1224). Nomenclature given for the Shigella and Salmonella structure, respectively: OMR (outer membrane ring), (inner membrane ring), Conn. (connector), Le (leg), OM (outer membrane ring), (IM (inner membrane ring). For the Salmonella density, the distribution of protein density along the central longitudinal section is shown as contour lines. Basal view of the Shigella needle complex base showing twelve spokes connecting the socket/cup with the IMR.

Figure 3. A structural building-block for the T3SS

Shown are the related structural domains of GspD, EscJ, EscC, and PrgH divided into two classes based on protein fold (PDB accession codes 3EZJ, 1YJ7, 3GR5, and 3GR0, respectively). A topology diagram is shown on the far right for each class to further illustrate the connectivity differences that are present in these folds despite the very similar three-dimensional appearance of the three-stranded β-sheet capped on one face by two interacting, anti-parallel helices. The location of these proteins in the basal body is roughly indicated on the left.