The type 2 secretion system (often referred to as the type II secretion system or by the initials T2SS) is a type of protein secretion machinery found in various species of Gram-negative bacteria, including many human pathogens such as Pseudomonas aeruginosa and Vibrio cholerae. The type II secretion system is one of six protein secretory systems commonly found in Gram-negative bacteria, along with the type I, type III, and type IV secretion systems, as well as the chaperone/usher pathway, the autotransporter pathway/type V secretion system, and the type VI secretion system (some bacteria also utilize the type VII secretion system). Like these other systems, the type II secretion system enables the transport of cytoplasmic proteins across the lipid bilayers that make up the cell membranes of Gram-negative bacteria. Secretion of proteins and effector molecules out of the cell plays a critical role in signaling other cells and in the invasion and parasitism of host cells.
Overview The type II secretion system is a membrane-bound protein complex found in Gram-negative bacteria that is used to secrete proteins found in the cytoplasm of the bacteria into the extracellular space outside of the cell. The type II secretion system is just one of many secretory systems found in Gram-negative bacteria and is used to secrete a variety of different proteins, including bacterial toxins and degradative enzymes such as proteases and lipases. These secreted proteins are generally associated with the breakdown of host tissues and therefore are often important in causing the symptoms associated with certain bacterial infections. Each bacterial cell may contain a number of type II secretion complexes, which are found embedded in the inner and outer membranes of the cell. Along with other secretory systems such as the chaperone/usher pathway and the type IV secretion system, type II secretion is a two-step process. The first step involves the Sec and Tat secretory pathways, which are responsible for transporting proteins across the inner membrane into the periplasm. For instance, the Sec pathway is used to transport structural components of the type II secretion system into the periplasm where they can then assemble, while both the Sec and Tat pathways are used to transport secretory proteins into the periplasm. Once these secretory proteins are located in the periplasm, the second step can then take place, whereby they are secreted across the outer membrane into the extracellular milieu.
Structure
Overall the type II secretion system is a large multiprotein machinery, made up of a number of distinct protein subunits known as the general secretory proteins (GSPs). The genes encoding these GSPs are usually found together in the genome in a single operon and many of these genes overlap. Each gene is named with a letter corresponding to the GSP that it encodes (for example the gspD gene encodes GspD) and studies indicate that between 12 and 15 of these genes are essential to the function of the type II secretion system. The GSPs are common among a number of different bacterial species and when they come together they form a complex that is structurally very similar to the type IV pili, an appendage that is also commonly found in gram negative bacteria. Overall the type II secretion system can be broken down into four main components. These are the outer membrane complex, the inner membrane complex, the secretion ATPase and the pseudopilus.
Outer membrane complex The outer membrane complex is made up largely by the secretin GspD. Secretins are β-barrels that are found in membrane where they form channels that allow substances to move in or out of cells. In the type II secretion system GspD creates a pore in the outer membrane of the bacterial cell through which proteins can be secreted. As a result, GspD is essential for the correct function system because without it secretory proteins cannot exit the cell. GspD is transported into the periplasm via the Sec translocon and is then inserted into the outer membrane. This insertion is not spontaneous however and is often reliant upon the β-barrel assembly machinery which ensures β-barrel proteins are folded correctly before insertion into the membrane. GspD is often found associated with the lipoprotein GspS. GspS is also transported into the periplasm using the Sec translocation machinery, at which point it is inserted into the inner layer of the outer membrane where it remains closely associated with GspD. It is thought that GspS plays an important role in the stabilization of the secretin GspD and helps prevent it from breaking down in the presence of highly degradative periplasmic enzymes. The translocation process of GspD to the outer membrane differs between GspD homologs. Escherichia coli secretins GspDα and GspDβ show distinct translocation mechanisms in vitro. The GspDβ forms its multimer on the inner membrane and interacts with GspS (pilotin), which disassembles GspDβ into its monomers. The monomers are guided through the peptidoglycan layer by GspS and forms the GspDβ multimer on the outer membrane together with GspS, forming a GspDβ-GspS complex. GspDα however, can translocate to the outer membrane without the assistance of pilotin in the presence of D-methionine. In the case of GspDα, it forms its multimer on the inner membrane, where it exists in an unstable form shifting between two confirmations. Reduced cross-linking in the peptidoglycan, induced by D-methionine, causes the formation of pores in the peptidoglycan layer which allows GspDα to translocate to the outer membrane, where it exists in a more stable and connected confirmation.
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