Type IV secretion system

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The bacterial type IV secretion system, also known as the type IV secretion system or the T4SS, is a secretion protein complex found in gram negative bacteria, gram positive bacteria, and archaea. It is able to transport proteins and DNA across the cell membrane. [1] The type IV secretion system is just one of many bacterial secretion systems. Type IV secretion systems are related to conjugation machinery which generally involve a single-step secretion system and the use of a pilus. [2] Type IV secretion systems are used for conjugation, DNA exchange with the extracellular space, and for delivering proteins to target cells. The type IV secretion system is divided into type IVA and type IVB based on genetic ancestry.

Contents

Notable instances of the type IV secretion system include the plasmid insertion into plants of Agrobacterium tumefaciens , the toxin delivery methods of Bordetella pertussis (whooping cough) and Legionella pneumophila (Legionnaires' disease), and the F sex pilus.

Function

The type IV secretion system is a protein complex found in prokaryotes used to transport DNA, proteins, or effector molecules from the cytoplasm to the extracellular space beyond the cell. [1] The type IV secretion system is related to prokaryotic conjugation machinery. [2] Type IV secretion systems are a highly versatile group, present in Gram positive bacteria, Gram negative bacteria, and archaea. They usually involve a single step which utilizes a pilus, though exceptions exist. [3]  

Type IV secretion systems are highly diverse, with a variety of functions and types due to different evolutionary paths. Primarily, type IV secretion systems are grouped based on structural and genetic similarity and are only distantly related to each other. Type IVA systems are similar to the VirB/D4 system of Agrobacterium tumefaciens. Type IVB systems are similar to the Dot/Icm systems found in intracellular pathogens such as Legionella pneumophila. The “other” type systems resemble neither IVA or IVB. [3] Types are genetically distinct and use separate sets of proteins, however, proteins between the sets have strong homologies to each other, which leads them to function similarly. [1]    

Type IV secretion systems are also classified by function into three main types. Conjugative systems: used for DNA transfer via cell to cell contact (a process called conjugation); DNA release and uptake systems: used to exchange DNA with the extracellular environment (a process called transformation); and effector systems: used to transfer proteins to target cells. [4] Conjugative as well as DNA release and uptake systems play an important role in horizontal gene transfer, which allows prokaryotes to adapt to their environment, such as, developing antibiotic resistance. [5] Effector systems allow for the interaction between microbes and larger organisms. The effector systems are used as a toxin delivery method by many human pathogens such as, Helicobacter pylori (stomach ulcers), whooping cough, and Legionnaires' disease. [1]

Structure

Currently, only the structure of type IVA secretion systems, which occur in gram-negative bacteria, is well described. It is composed of 12 protein subunits, VirB1 - VirB11 and VirD4, analogies of which exist in all type IVA systems. [1] The Type IV secretion system’s components can be separated into 3 groups: the translocation channel scaffold, the ATPases, and the pilus.

Type IV Secretion system T4SS.svg
Type IV Secretion system

The translocation channel scaffold is the portion of the machinery that creates the channel between extracellular space and the cytoplasm through the inner and outer membranes, and contains VirB6 - VirB10. The core complex of the scaffold is composed of 14 copies of VirB7, VirB9, and VirB10 which form a cylindrical channel that spans both membranes and connects the cytoplasm to the extracellular space. [6]

A single protein, VirB10 is integral in both the inner and outer membranes. It inserts into the outer membrane using an α-helical barrel structure which helps form a channel between the two membranes. [7] There is an opening on the cytoplasmic end of the channel which is followed by a large chamber and a second opening. The second opening requires a conformational change to allow substrate passage from the cytoplasm into the channel. [1] Either VirB6 or VirB8 is believed to form the inner membrane pore, as they are integral proteins on the inner membrane and have direct contact with the substrate. [8]

The ATPases consist of VirB4, VirB11, and VirD4, which drive the substrate motion through the channel and provide the system with energy. VirB11 belongs to a class of transmembrane transporters called “traffic ATPases”. VirB4 is not well characterized. [9] [1]

The pilus is composed of VirB2 and VirB5, with VirB2 being the major component. [1] In A. tumefaciens , the pilus is 8-12 nm in diameter, and less than one µm in length. F pili, another commonly examined type of pilus, are much longer with a length of 2-20 µm. [2]

Mechanism

Due to the wide variety of type IV secretion systems in both origin and function, it is difficult to state much mechanistically about the group as a whole.

In general, after DNA is packaged in a conjugative system it is recruited by ATPase analogues to the VirD4 coupling protein, then translocated through the pilus. [3] In A. tumefaciens specifically, the DNA passes through a characterized chain of enzymes before reaching the pilus. The DNA is recruited by VirD4, then VirB11, then to the intermembrane proteins (VirB6, and VirB8), moved to VirB9, and finally sent to the pilus (VirB2). [10] [1]

Related Research Articles

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<span class="mw-page-title-main">Pilus</span> A proteinaceous hair-like appendage on the surface of bacteria

A pilus is a hair-like appendage found on the surface of many bacteria and archaea. The terms pilus and fimbria can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All conjugative pili are primarily composed of pilin – fibrous proteins, which are oligomeric.

<span class="mw-page-title-main">Digestion</span> Biological process of breaking down food

Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.

<span class="mw-page-title-main">Secretion</span> Controlled release of substances by cells or tissues

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<span class="mw-page-title-main">Transformation (genetics)</span> Genetic alteration of a cell by uptake of genetic material from the environment

In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to take place, the recipient bacterium must be in a state of competence, which might occur in nature as a time-limited response to environmental conditions such as starvation and cell density, and may also be induced in a laboratory.

<i>Agrobacterium tumefaciens</i> Bacterium, genetic engineering tool

Agrobacterium radiobacter is the causal agent of crown gall disease in over 140 species of eudicots. It is a rod-shaped, Gram-negative soil bacterium. Symptoms are caused by the insertion of a small segment of DNA, from a plasmid into the plant cell, which is incorporated at a semi-random location into the plant genome. Plant genomes can be engineered by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors.

<span class="mw-page-title-main">Ti plasmid</span>

A tumour inducing (Ti) plasmid is a plasmid found in pathogenic species of Agrobacterium, including A. tumefaciens, A. rhizogenes, A. rubi and A. vitis.

Pilin refers to a class of fibrous proteins that are found in pilus structures in bacteria. These structures can be used for the exchange of genetic material, or as a cell adhesion mechanism. Although not all bacteria have pili or fimbriae, bacterial pathogens often use their fimbriae to attach to host cells. In Gram-negative bacteria, where pili are more common, individual pilin molecules are linked by noncovalent protein-protein interactions, while Gram-positive bacteria often have polymerized LPXTG pilin.

<span class="mw-page-title-main">Type III secretion system</span> Protein appendage

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Gabriel Waksman FMedSci, FRS, is Courtauld professor of biochemistry and molecular biology at University College London (UCL), and professor of structural and molecular biology at Birkbeck College, University of London. He is the director of the Institute of Structural and Molecular Biology (ISMB) at UCL and Birkbeck, head of the Department of Structural and Molecular Biology at UCL, and head of the Department of Biological Sciences at Birkbeck.

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The type 2 secretion system 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. 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.

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<span class="mw-page-title-main">Bacterial secretion system</span> Protein complexes present on the cell membranes of bacteria for secretion of substances

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