Secretion

Last updated
Secretory mechanism.jpg

Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. [1] Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

Contents

Secretion in bacterial species means the transport or translocation of effector molecules. For example: proteins, enzymes or toxins (such as cholera toxin in pathogenic bacteria e.g. Vibrio cholerae ) from across the interior (cytoplasm or cytosol) of a bacterial cell to its exterior. Secretion is a very important mechanism in bacterial functioning and operation in their natural surrounding environment for adaptation and survival.

In eukaryotic cells

Porosome Porosome for wiki-2.jpg
Porosome

Mechanism

Eukaryotic cells, including human cells, have a highly evolved process of secretion. Proteins targeted for the outside are synthesized by ribosomes docked to the rough endoplasmic reticulum (ER). As they are synthesized, these proteins translocate into the ER lumen, where they are glycosylated and where molecular chaperones aid protein folding. Misfolded proteins are usually identified here and retrotranslocated by ER-associated degradation to the cytosol, where they are degraded by a proteasome. The vesicles containing the properly folded proteins then enter the Golgi apparatus.

In the Golgi apparatus, the glycosylation of the proteins is modified and further post-translational modifications, including cleavage and functionalization, may occur. The proteins are then moved into secretory vesicles which travel along the cytoskeleton to the edge of the cell. More modification can occur in the secretory vesicles (for example insulin is cleaved from proinsulin in the secretory vesicles).

Eventually, there is vesicle fusion with the cell membrane at porosomes, by a process called exocytosis, dumping its contents out of the cell's environment. [2]

Strict biochemical control is maintained over this sequence by usage of a pH gradient: the pH of the cytosol is 7.4, the ER's pH is 7.0, and the cis-golgi has a pH of 6.5. Secretory vesicles have pHs ranging between 5.0 and 6.0; some secretory vesicles evolve into lysosomes, which have a pH of 4.8.

Nonclassical secretion

There are many proteins like FGF1 (aFGF), FGF2 (bFGF), interleukin-1 (IL1) etc. which do not have a signal sequence. They do not use the classical ER-Golgi pathway. These are secreted through various nonclassical pathways.

At least four nonclassical (unconventional) protein secretion pathways have been described. [3] They include:

  • direct protein translocation across the plasma membrane likely through membrane transport proteins
  • blebbing
  • lysosomal secretion
  • release via exosomes derived from multivesicular bodies

In addition, proteins can be released from cells by mechanical or physiological wounding [4] and through non-lethal, transient oncotic pores in the plasma membrane induced by washing cells with serum-free media or buffers. [5]

In human tissues

Many human cell types have the ability to be secretory cells. They have a well-developed endoplasmic reticulum, and Golgi apparatus to fulfill this function. Tissues that produce secretions include the gastrointestinal tract which secretes digestive enzymes and gastric acid, the lungs which secrete surfactants, and sebaceous glands which secrete sebum to lubricate the skin and hair. Meibomian glands in the eyelid secrete meibum to lubricate and protect the eye.

In gram-negative bacteria

Secretion is not unique to eukaryotes – it is also present in bacteria and archaea as well. ATP binding cassette (ABC) type transporters are common to the three domains of life. Some secreted proteins are translocated across the cytoplasmic membrane by the SecYEG translocon, one of two translocation systems, which requires the presence of an N-terminal signal peptide on the secreted protein. Others are translocated across the cytoplasmic membrane by the twin-arginine translocation pathway (Tat). Gram-negative bacteria have two membranes, thus making secretion topologically more complex. There are at least six specialized secretion systems in gram-negative bacteria. Many secreted proteins are particularly important in bacterial pathogenesis. [6]

Type I secretion system (T1SS or TOSS)

T1SS.svg

Type I secretion is a chaperone dependent secretion system employing the Hly and Tol gene clusters. The process begins as a leader sequence on the protein to be secreted is recognized by HlyA and binds HlyB on the membrane. This signal sequence is extremely specific for the ABC transporter. The HlyAB complex stimulates HlyD which begins to uncoil and reaches the outer membrane where TolC recognizes a terminal molecule or signal on HlyD. HlyD recruits TolC to the inner membrane and HlyA is excreted outside of the outer membrane via a long-tunnel protein channel.

Type I secretion system transports various molecules, from ions, drugs, to proteins of various sizes (20 – 900 kDa). The molecules secreted vary in size from the small Escherichia coli peptide colicin V, (10 kDa) to the Pseudomonas fluorescens cell adhesion protein LapA of 520 kDa. [7] The best characterized are the RTX toxins and the lipases. Type I secretion is also involved in export of non-proteinaceous substrates like cyclic β-glucans and polysaccharides.

T2SS.svg

Type II secretion system (T2SS)

Proteins secreted through the type II system, or main terminal branch of the general secretory pathway, depend on the Sec or Tat system for initial transport into the periplasm. Once there, they pass through the outer membrane via a multimeric (12–14 subunits) complex of pore forming secretin proteins. In addition to the secretin protein, 10–15 other inner and outer membrane proteins compose the full secretion apparatus, many with as yet unknown function. Gram-negative type IV pili use a modified version of the type II system for their biogenesis, and in some cases certain proteins are shared between a pilus complex and type II system within a single bacterial species.

Type III secretion system (T3SS or TTSS)

T3SS.svg

It is homologous to the basal body in bacterial flagella. It is like a molecular syringe through which a bacterium (e.g. certain types of Salmonella , Shigella , Yersinia , Vibrio ) can inject proteins into eukaryotic cells. The low Ca2+ concentration in the cytosol opens the gate that regulates T3SS. One such mechanism to detect low calcium concentration has been illustrated by the lcrV (Low Calcium Response) antigen utilized by Yersinia pestis , which is used to detect low calcium concentrations and elicits T3SS attachment. The Hrp system in plant pathogens inject harpins and pathogen effector proteins through similar mechanisms into plants. This secretion system was first discovered in Yersinia pestis and showed that toxins could be injected directly from the bacterial cytoplasm into the cytoplasm of its host's cells rather than simply be secreted into the extracellular medium. [8]

Type IV secretion system (T4SS or TFSS)

T4SS
T4SS.svg
Type IV secretion system
Identifiers
SymbolT4SS
Pfam PF07996
InterPro IPR012991
SCOP2 1gl7 / SCOPe / SUPFAM
TCDB 3.A.7
OPM superfamily 215
OPM protein 3jqo
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

It is homologous to conjugation machinery of bacteria, the conjugative pili. It is capable of transporting both DNA and proteins. It was discovered in Agrobacterium tumefaciens, which uses this system to introduce the T-DNA portion of the Ti plasmid into the plant host, which in turn causes the affected area to develop into a crown gall (tumor). Helicobacter pylori uses a type IV secretion system to deliver CagA into gastric epithelial cells, which is associated with gastric carcinogenesis. [9] Bordetella pertussis , the causative agent of whooping cough, secretes the pertussis toxin partly through the type IV system. Legionella pneumophila , the causing agent of legionellosis (Legionnaires' disease) utilizes a type IVB secretion system, known as the icm/dot (intracellular multiplication / defect in organelle trafficking genes) system, to translocate numerous effector proteins into its eukaryotic host. [10] The prototypic Type IVA secretion system is the VirB complex of Agrobacterium tumefaciens . [11]

Protein members of this family are components of the type IV secretion system. They mediate intracellular transfer of macromolecules via a mechanism ancestrally related to that of bacterial conjugation machineries. [12] [13]

Function

The Type IV secretion system (T4SS) is the general mechanism by which bacterial cells secrete or take up macromolecules. Their precise mechanism remains unknown. T4SS is encoded on Gram-negative conjugative elements in bacteria. T4SS are cell envelope-spanning complexes, or, in other words, 11–13 core proteins that form a channel through which DNA and proteins can travel from the cytoplasm of the donor cell to the cytoplasm of the recipient cell. T4SS also secrete virulence factor proteins directly into host cells as well as taking up DNA from the medium during natural transformation. [14]

Structure

As shown in the above figure, TraC, in particular consists of a three helix bundle and a loose globular appendage. [13]

Interactions

T4SS has two effector proteins: firstly, ATS-1, which stands for Anaplasma translocated substrate 1, and secondly AnkA, which stands for ankyrin repeat domain-containing protein A. Additionally, T4SS coupling proteins are VirD4, which bind to VirE2. [15]

Type V secretion system (T5SS)

T5SS.svg

Also called the autotransporter system, [16] type V secretion involves use of the Sec system for crossing the inner membrane. Proteins which use this pathway have the capability to form a beta-barrel with their C-terminus which inserts into the outer membrane, allowing the rest of the peptide (the passenger domain) to reach the outside of the cell. Often, autotransporters are cleaved, leaving the beta-barrel domain in the outer membrane and freeing the passenger domain. Some researchers believe remnants of the autotransporters gave rise to the porins which form similar beta-barrel structures.[ citation needed ] A common example of an autotransporter that uses this secretion system is the Trimeric Autotransporter Adhesins. [17]

Type VI secretion system (T6SS)

Type VI secretion systems were originally identified in 2006 by the group of John Mekalanos at the Harvard Medical School (Boston, USA) in two bacterial pathogens, Vibrio cholerae and Pseudomonas aeruginosa . [18] [19] These were identified when mutations in the Hcp and VrgG genes in Vibrio cholerae led to decreased virulence and pathogenicity. Since then, Type VI secretion systems have been found in a quarter of all proteobacterial genomes, including animal, plant, human pathogens, as well as soil, environmental or marine bacteria. [20] [21] While most of the early studies of Type VI secretion focused on its role in the pathogenesis of higher organisms, more recent studies suggested a broader physiological role in defense against simple eukaryotic predators and its role in inter-bacteria interactions. [22] [23] The Type VI secretion system gene clusters contain from 15 to more than 20 genes, two of which, Hcp and VgrG, have been shown to be nearly universally secreted substrates of the system. Structural analysis of these and other proteins in this system bear a striking resemblance to the tail spike of the T4 phage, and the activity of the system is thought to functionally resemble phage infection. [24]

Release of outer membrane vesicles

In addition to the use of the multiprotein complexes listed above, Gram-negative bacteria possess another method for release of material: the formation of bacterial outer membrane vesicles. [25] Portions of the outer membrane pinch off, forming nano-scale spherical structures made of a lipopolysaccharide-rich lipid bilayer enclosing periplasmic materials, and are deployed for membrane vesicle trafficking to manipulate environment or invade at host–pathogen interface. Vesicles from a number of bacterial species have been found to contain virulence factors, some have immunomodulatory effects, and some can directly adhere to and intoxicate host cells. release of vesicles has been demonstrated as a general response to stress conditions, the process of loading cargo proteins seems to be selective. [26]

In gram-positive bacteria

In some Staphylococcus and Streptococcus species, the accessory secretory system handles the export of highly repetitive adhesion glycoproteins.

See also

Related Research Articles

Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to the N-acetylmuramic acid is an oligopeptide chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material.

<span class="mw-page-title-main">Vesicle (biology and chemistry)</span> Any small, fluid-filled, spherical organelle enclosed by a membrane

In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, the vesicles are called unilamellar liposomes; otherwise they are called multilamellar liposomes. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.

<span class="mw-page-title-main">Exocytosis</span> Active transport and bulk transport in which a cell transports molecules out of the cell

Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

<i>Moraxella catarrhalis</i> Species of bacterium

Moraxella catarrhalis is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the infection of the host cell by sticking to the host cell using trimeric autotransporter adhesins.

A secretory protein is any protein, whether it be endocrine or exocrine, which is secreted by a cell. Secretory proteins include many hormones, enzymes, toxins, and antimicrobial peptides. Secretory proteins are synthesized in the endoplasmic reticulum.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

<span class="mw-page-title-main">Type III secretion system</span> Bacterial virulence factor

The type III secretion system is one of the bacterial secretion systems used by bacteria to secrete their effector proteins into the host's cells to promote virulence and colonisation. While the type III secretion system has been widely regarded as equivalent to the injectisome, many argue that the injectisome is only part of the type III secretion system, which also include structures like the flagellar export apparatus. The T3SS is a needle-like protein complex found in several species of pathogenic gram-negative bacteria.

<span class="mw-page-title-main">Autotransporter family</span>

In molecular biology, an autotransporter domain is a structural domain found in some bacterial outer membrane proteins. The domain is always located at the C-terminal end of the protein and forms a beta-barrel structure. The barrel is oriented in the membrane such that the N-terminal portion of the protein, termed the passenger domain, is presented on the cell surface. These proteins are typically virulence factors, associated with infection or virulence in pathogenic bacteria.

The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.

<span class="mw-page-title-main">Trimeric autotransporter adhesin</span> Proteins found on the outer membrane of Gram-negative bacteria

In molecular biology, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs also go by another name, oligomeric coiled-coil adhesins, which is shortened to OCAs. In essence, they are virulence factors, factors that make the bacteria harmful and infective to the host organism.

Autodisplay is a genetic engineering technique which is used to insert a protein of interest on the outer surface of gram-negative bacteria. This is accomplished by attaching the protein of interest to a protein which is known to localize to the surface of the bacterial outer membrane. First introduced in the 1990s, the technique is now widely used in research science and in biotechnology to manipulate bacteria for protein studies, drug discovery, and vaccine development.

Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.

Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory cell. It takes place in the form of Golgi membrane-bound micro-sized vesicles, termed membrane vesicles (MVs).

<span class="mw-page-title-main">Outer membrane vesicle</span> Vesicles released from the outer membranes of Gram-negative bacteria

Outer membrane vesicles (OMVs) are vesicles released from the outer membranes of Gram-negative bacteria. While Gram-positive bacteria release vesicles as well those vesicles fall under the broader category of bacterial membrane vesicles (MVs). OMVs were the first MVs to be discovered, and are distinguished from outer inner membrane vesicles (OIMVS), which are gram-negative baterial vesicles containing portions of both the outer and inner bacterial membrane. Outer membrane vesicles were first discovered and characterized using transmission-electron microscopy by Indian Scientist Prof. Smriti Narayan Chatterjee and J. Das in 1966-67. OMVs are ascribed the functionality to provide a manner to communicate among themselves, with other microorganisms in their environment and with the host. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins and allied virulence molecules. This communication happens in microbial cultures in oceans, inside animals, plants and even inside the human body.

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda.

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.

Contact-dependent growth inhibition (CDI) is a phenomenon where a bacterial cell may deliver a polymorphic toxin molecule into neighbouring bacterial cells upon direct cell-cell contact, causing growth arrest or cell death.

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

Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.

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. 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. 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.

Type VII secretion systems are bacterial secretion systems first observed in the phyla Actinomycetota and Bacillota. Bacteria use such systems to transport, or secrete, proteins into the environment. The bacterial genus Mycobacterium uses type VII secretion systems (T7SS) to secrete proteins across their cell envelope. The first T7SS system discovered was the ESX-1 System.

References

[27]

  1. ↑ Lee JS, Jeremic A, Shin L, Cho WJ, Chen X, Jena BP (July 2012). "Neuronal porosome proteome: Molecular dynamics and architecture". Journal of Proteomics. 75 (13): 3952–62. doi:10.1016/j.jprot.2012.05.017. PMC   4580231 . PMID   22659300.
  2. ↑ Anderson LL (2006). "Discovery of the 'porosome'; the universal secretory machinery in cells". Journal of Cellular and Molecular Medicine. 10 (1): 126–31. doi:10.1111/j.1582-4934.2006.tb00294.x. PMC   3933105 . PMID   16563225.
  3. ↑ Nickel W, Seedorf M (2008). "Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells". Annual Review of Cell and Developmental Biology. 24: 287–308. doi:10.1146/annurev.cellbio.24.110707.175320. PMID   18590485.
  4. ↑ McNeil PL, Steinhardt RA (2003). "Plasma membrane disruption: repair, prevention, adaptation". Annual Review of Cell and Developmental Biology. 19: 697–731. doi:10.1146/annurev.cellbio.19.111301.140101. PMID   14570587.
  5. ↑ Chirico WJ (October 2011). "Protein release through nonlethal oncotic pores as an alternative nonclassical secretory pathway". BMC Cell Biology. 12: 46. doi: 10.1186/1471-2121-12-46 . PMC   3217904 . PMID   22008609.
  6. ↑ Wooldridge, K, ed. (2009). Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis. Caister Academic Press. ISBN   978-1-904455-42-4.[ page needed ]
  7. ↑ Boyd CD, Smith TJ, El-Kirat-Chatel S, Newell PD, Dufrêne YF, O'Toole GA (August 2014). "Structural features of the Pseudomonas fluorescens biofilm adhesin LapA required for LapG-dependent cleavage, biofilm formation, and cell surface localization". Journal of Bacteriology. 196 (15): 2775–88. doi:10.1128/JB.01629-14. PMC   4135675 . PMID   24837291.
  8. ↑ Salyers, A. A. & Whitt, D. D. (2002). Bacterial Pathogenesis: A Molecular Approach, 2nd ed., Washington, D.C.: ASM Press. ISBN   1-55581-171-X [ page needed ]
  9. ↑ Hatakeyama M, Higashi H (December 2005). "Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis". Cancer Science. 96 (12): 835–43. doi: 10.1111/j.1349-7006.2005.00130.x . PMID   16367902. S2CID   5721063.
  10. ↑ Cascales E, Christie PJ (November 2003). "The versatile bacterial type IV secretion systems". Nature Reviews. Microbiology. 1 (2): 137–49. doi:10.1038/nrmicro753. PMC   3873781 . PMID   15035043.
  11. ↑ Christie PJ, Atmakuri K, Krishnamoorthy V, Jakubowski S, Cascales E (2005). "Biogenesis, architecture, and function of bacterial type IV secretion systems". Annual Review of Microbiology. 59: 451–85. doi:10.1146/annurev.micro.58.030603.123630. PMC   3872966 . PMID   16153176.
  12. ↑ Christie PJ (November 2004). "Type IV secretion: the Agrobacterium VirB/D4 and related conjugation systems". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1694 (1–3): 219–34. doi:10.1016/j.bbamcr.2004.02.013. PMC   4845649 . PMID   15546668.
  13. 1 2 Yeo HJ, Yuan Q, Beck MR, Baron C, Waksman G (December 2003). "Structural and functional characterization of the VirB5 protein from the type IV secretion system encoded by the conjugative plasmid pKM101". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 15947–52. Bibcode:2003PNAS..10015947Y. doi: 10.1073/pnas.2535211100 . JSTOR   3149111. PMC   307673 . PMID   14673074.
  14. ↑ Lawley TD, Klimke WA, Gubbins MJ, Frost LS (July 2003). "F factor conjugation is a true type IV secretion system". FEMS Microbiology Letters. 224 (1): 1–15. doi: 10.1016/S0378-1097(03)00430-0 . PMID   12855161.
  15. ↑ Rikihisa Y, Lin M, Niu H (September 2010). "Type IV secretion in the obligatory intracellular bacterium Anaplasma phagocytophilum". Cellular Microbiology. 12 (9): 1213–21. doi:10.1111/j.1462-5822.2010.01500.x. PMC   3598623 . PMID   20670295.
  16. ↑ Thanassi DG, Stathopoulos C, Karkal A, Li H (2005). "Protein secretion in the absence of ATP: the autotransporter, two-partner secretion and chaperone/usher pathways of gram-negative bacteria (review)". Molecular Membrane Biology. 22 (1–2): 63–72. doi:10.1080/09687860500063290. PMID   16092525. S2CID   2708575.
  17. ↑ Gerlach RG, Hensel M (October 2007). "Protein secretion systems and adhesins: the molecular armory of Gram-negative pathogens". International Journal of Medical Microbiology. 297 (6): 401–15. doi:10.1016/j.ijmm.2007.03.017. PMID   17482513.
  18. ↑ Pukatzki S, Ma AT, Sturtevant D, Krastins B, Sarracino D, Nelson WC, Heidelberg JF, Mekalanos JJ (January 2006). "Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system". Proceedings of the National Academy of Sciences of the United States of America. 103 (5): 1528–33. Bibcode:2006PNAS..103.1528P. doi: 10.1073/pnas.0510322103 . JSTOR   30048406. PMC   1345711 . PMID   16432199.
  19. ↑ Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman AL, Joachimiak G, Ordoñez CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ (June 2006). "A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus". Science. 312 (5779): 1526–30. Bibcode:2006Sci...312.1526M. doi:10.1126/science.1128393. PMC   2800167 . PMID   16763151.
  20. ↑ Bingle LE, Bailey CM, Pallen MJ (February 2008). "Type VI secretion: a beginner's guide" (PDF). Current Opinion in Microbiology. 11 (1): 3–8. doi:10.1016/j.mib.2008.01.006. PMID   18289922.
  21. ↑ Cascales E (August 2008). "The type VI secretion toolkit". EMBO Reports. 9 (8): 735–41. doi:10.1038/embor.2008.131. PMC   2515208 . PMID   18617888.
  22. ↑ Schwarz S, Hood RD, Mougous JD (December 2010). "What is type VI secretion doing in all those bugs?". Trends in Microbiology. 18 (12): 531–7. doi:10.1016/j.tim.2010.09.001. PMC   2991376 . PMID   20961764.
  23. ↑ Coulthurst SJ (2013). "The Type VI secretion system - a widespread and versatile cell targeting system". Research in Microbiology. 164 (6): 640–54. doi:10.1016/j.resmic.2013.03.017. PMID   23542428.
  24. ↑ Silverman JM, Brunet YR, Cascales E, Mougous JD (2012). "Structure and regulation of the type VI secretion system". Annual Review of Microbiology. 66: 453–72. doi:10.1146/annurev-micro-121809-151619. PMC   3595004 . PMID   22746332.
  25. ↑ Kuehn MJ, Kesty NC (November 2005). "Bacterial outer membrane vesicles and the host–pathogen interaction". Genes & Development. 19 (22): 2645–55. doi: 10.1101/gad.1299905 . PMID   16291643.
  26. ↑ McBroom AJ, Kuehn MJ (January 2007). "Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response". Molecular Microbiology. 63 (2): 545–58. doi:10.1111/j.1365-2958.2006.05522.x. PMC   1868505 . PMID   17163978.
  27. ↑ Z. Esna Ashari, N. Dasgupta, K. Brayton & S. Broschat, “An optimal set of features for predicting type IV secretion system effector proteins for a subset of species based on a multi-level feature selection approach”, PLOS ONE Journal, 2018, 13, e0197041. (doi.org/10.1371/journal.pone.0197041.)

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.