Assembly, structure, function and regulation of type III secretion systems

Abstract

Type III secretion systems (T3SSs) are protein transport nanomachines that are found in Gram-negative bacterial pathogens and symbionts. Resembling molecular syringes, T3SSs form channels that cross the bacterial envelope and the host cell membrane, which enable bacteria to inject numerous effector proteins into the host cell cytoplasm and establish trans-kingdom interactions with diverse hosts. Recent advances in cryo-electron microscopy and integrative imaging have provided unprecedented views of the architecture and structure of T3SSs. Furthermore, genetic and molecular analyses have elucidated the functions of many effectors and key regulators of T3SS assembly and secretion hierarchy, which is the sequential order by which the protein substrates are secreted. As essential virulence factors, T3SSs are attractive targets for vaccines and therapeutics. This Review summarizes our current knowledge of the structure and function of this important protein secretion machinery. A greater understanding of T3SSs should aid mechanism-based drug design and facilitate their manipulation for biotechnological applications.

Advances on Vibrio parahaemolyticus research in the postgenomic era

“…and Pseudomonas aeruginosa ). Among the conserved features of the T3SS core structural components, the T3SS needle filaments of plant pathogens, termed Hrp pili, differ from those of animal pathogens in that their protrusions are much longer . The needle architectures of T3SS2 extending from V. parahaemolyticus have not been determined.…”

“…In general, T3SS secretion is hierarchically controlled to ensure processes from needle assembly to the efficient translocation of effectors into target cells . The substrates for T3SS secretion are generally divided into three categories: early (needle and inner rod proteins), middle (translocator proteins), and late (effector proteins) substrates . First, T3SS releases early substrates to create a tubular needle filament.…”

“…In turn, effector proteins (as late substrates) are secreted inside host cells. The gatekeeper protein SctW is involved in the switching from middle to late substrates . The gatekeeper interacts with the export‐apparatus protein SctV, which may favor the secretion of translocators, but not of effectors .…”

Structure of the Core of the Type Three Secretion System Export Apparatus

“…A combination of many structural techniques has led to atomic models for most of the soluble components, the circularly symmetric rings that compose the majority of the basal body and for both flagellar rod/hook/flagellum and injectisome needle 4 . However, the EA remains poorly understood, with the topology and number of membrane helices of the three most hydrophobic proteins ( Fig.…”

“…Both of these classes are associated with the pathogenicity of a wide range of clinically relevant bacteria 3 . T3SS are assembled from a basal body consisting of a series of concentric oligomeric protein rings across the inner and outer membranes, from which the helical hook and flagellum or needle structures project 2,4,5 . Proteins associated with the cytoplasmic face of the basal body select proteins for export that are then transferred to a set of 5 membrane associated proteins roughly located to center of the inner-membrane ring.…”