Type II secretion system
Bacterial type II and III secretion system protein | |||||||||
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Identifiers | |||||||||
Symbol | Secretin | ||||||||
TCDB | 3.A.5 | ||||||||
OPM superfamily | 348 | ||||||||
OPM protein | 5wln | ||||||||
Membranome | 430 | ||||||||
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The type 2 secretion system (often referred to as the type II secretion system or by the initials T2SS) is a type of protein
Overview
The type II secretion system is a membrane-bound
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
Structure
Overall the type II secretion system is a large multiprotein machinery, made up of a number of distinct protein
Outer Membrane Complex
The outer membrane complex is made up largely by the secretin GspD.[8] Secretins are β-barrels that are found in membrane where they form channels that allow substances to move in or out of cells.[9] 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.[10]
GspD is often found associated with the
Inner Membrane Complex
The inner membrane complex is made up of several different Gsp proteins which are embedded in the inner membrane. Like the outer membrane secretin GspD these proteins are transported into the periplasm via the Sec translocation pathway before being inserted into the inner membrane. Four different proteins make up the inner membrane complex; these are GspC, GspF, GspL and GspM.[5]
Each of these individual subunits plays a slightly different role. GspC for instance has been shown to interact with GspD. This interaction helps gate the type II secretion system and only when this gate is open are secretory proteins able to enter the system and be pumped out of the cell. Importantly, when associated together, GspC, GspL and GspM help protect each other from proteolytic enzymes that would otherwise degrade them. Unlike the other proteins that make up the inner membrane complex GspF is a
Secretion ATPase
The secretion ATPase, GspE, is an ATPase which is found closely associated with the inner membrane complex on the cytoplasmic side of the inner membrane.
Pseudopilus
The pseudopilus is found in the periplasm but does not extend out through the secretin GspD into the extracellular milieu. Its name it derived from the fact that it is made up of a number of
The major pseudopilin present in the pseudopilus is GspG. The pseudopilus forms when the individual pseudopilin subunits
Mechanism
Secretion of proteins via the type II secretion system occurs in a very specific way and is largely uniform among different species of bacteria. This mechanism can be broken down into several steps:
- Exoproteins, or proteins that are to be secreted, are first transported across the inner membrane and into the periplasm via the Sec translocation machinery. These exoproteins will exist here in the periplasm secretion until the type II secretion system is activated.
- Pre-pseudopilins are also transported from the cytoplasm into the periplasm via the Sec translocation machinery. Once in the periplasm they are cleaved by the pre-pilin peptidase GspO and converted into mature pseudopilins. The mature pseudopilins can then insert themselves into the inner membrane where they will exist until pseudopilus assembly occurs.
- The secretion ATPase GspE will then bind and hydrolyze ATP and the energy produced is used to power the formation of the pseudopilus. GspE is located in the cytoplasm but remains associated with the inner membrane complex via interactions with both GspL and GspF.
- When activated, the exoproteins previously transported into the periplasm are able to enter the secretion machinery. It is not fully understood how these exoproteins are selected for, but it is believed the interaction between GspC and GspD plays an important role.
- The assembly of the pseudopilus then forces the exoproteins out through the secretin GspD and into the extracellular milieu. This secretin forms a hydrophilic channel in the outer membrane which allows the proteins to exit the cell.
- Once outside of the cell the secreted exoproteins can then carry out their intended effects. Some of these for instance may be involved in signallingand others may act as virulence factors that help promote infection.
It is believed that quorum sensing plays a key role in controlling the activation of the type II secretion system and the initiation of exoprotein release.[6] Specifically quorum sensing helps regulate the transcription of the genes encoding these exoproteins and ensures that they are only produced when other like bacteria are nearby and environmental conditions are conducive to survival and infection.