Autotransporter domain

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Autotransporter beta-domain

PDB 1uyn EBI.jpg

Structure of the autotransporter domain NalP from Neisseria meningitidis. PDB entry 1uyn [1]
Identifiers
Symbol Autotransporter
Pfam PF03797
InterPro IPR005546
PROSITE PDOC51208
SCOP 1uyn
SUPERFAMILY 1uyn
TCDB 1.B.12
OPM superfamily 28
OPM protein 1uyo

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.

Protein domain

A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins.

Bacterial outer membrane

The bacterial outer membrane is found in gram-negative bacteria. Its composition is distinct from that of the inner cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and in some bacteria such as E. coli it is linked to the cell's peptidoglycan by Braun's lipoprotein.

Contents

The name autotransporter derives from an initial understanding that the protein was self-sufficient in transporting the passenger domain through the outermembrane. This view has since been challenged by Benz and Schmidt. [2]

Secretion of polypeptide chains through the outer membrane of Gram-negative bacteria can occur via a number of different pathways. The type V(a), or autotransporter, secretion pathway constitutes the largest number of secreted virulence factors of any one of the seven known types of secretion in Gram-negative bacteria. This secretion pathway is exemplified by the prototypical IgA1 Protease of Neisseria gonorrhoeae. [3] The protein is directed to the inner membrane by a signal peptide transported across the inner membrane via the Sec machinery. Once in the periplasm, the autotransporter domain inserts into the outer membrane. The passenger domain is passed through the center of the autotransporter domain to be presented on the outside of the cell, however the mechanism by which this occurs remains unclear. [4]

Gram-negative bacteria group of bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation

Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane.

A signal peptide is a short peptide present at the N-terminus of the majority of newly synthesized proteins that are destined towards the secretory pathway. These proteins include those that reside either inside certain organelles, secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, the majority of type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved.

Periplasm

The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the periplasmic space in gram-negative bacteria. Using cryo-electron microscopy it has been found that a much smaller periplasmic space is also present in gram-positive bacteria.

The C-terminal translocator domain corresponds to an outer membrane beta-barrel domain. The N-terminal passenger domain is translocated across the membrane, and may or may not be cleaved from the translocator domain. [5] In those proteins where the cleavage is auto-catalytic, the peptidase domains belong to MEROPS peptidase families S6 and S8. Passenger domains structurally characterized to date have been shown to be dominated by a protein fold known as a beta helix, typified by pertactin. The folding of this domain is thought to be intrinsically linked to its method of outer membrane translocation.

Beta helix

A beta helix is a tandem protein repeat structure formed by the association of parallel beta strands in a helical pattern with either two or three faces. The beta helix is a type of solenoid protein domain. The structure is stabilized by inter-strand hydrogen bonds, protein-protein interactions, and sometimes bound metal ions. Both left- and right-handed beta helices have been identified. Double stranded beta-helices are also very common features of proteins and are generally synonymous with jelly roll folds.

Pertactin

In molecular biology, pertactin (PRN) is a highly immunogenic virulence factor of Bordetella pertussis, the bacterium that causes pertussis. Specifically, it is an outer membrane protein that promotes adhesion to tracheal epithelial cells. PRN is purified from Bordetella pertussis and is used for the vaccine production as one of the important components of acellular pertussis vaccine.

See also

Trimeric Autotransporter Adhesins (TAA)

Related Research Articles

Transmembrane protein protein spanning across a biological membrane

A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane to which it is permanently attached. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane.

Lipopolysaccharide chemical compound

Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria.

Secretion is the movement of material from one point to another, e.g. 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 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.

Porin (protein)

Porins are beta barrel proteins that cross a cellular membrane and act as a pore, through which molecules can diffuse. Unlike other membrane transport proteins, porins are large enough to allow passive diffusion, i.e., they act as channels that are specific to different types of molecules. They are present in the outer membrane of gram-negative bacteria and some gram-positive Mycobacteria, the outer membrane of mitochondria, and the outer chloroplast membrane.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually the host they are infecting or living in. Adhesins are a type of virulence factor.

Bacterial display is a protein engineering technique used for in vitro protein evolution. Libraries of polypeptides displayed on the surface of bacteria can be screened using flow cytometry or iterative selection procedures (biopanning). This protein engineering technique allows us to link the function of a protein with the gene that encodes it. Bacterial display can be used to find target proteins with desired properties and can be used to make affinity ligands which are cell-specific. This system can be used in many applications including the creation of novel vaccines, the identification of enzyme substrates and finding the affinity of a ligand for its target protein.

Virulence factors are molecules produced by bacteria, viruses, fungi, and protozoa that add to their effectiveness and enable them to achieve the following:

The twin-arginine translocation pathway is a protein export, or secretion pathway found in plants, bacteria, and archaea. In contrast to the Sec pathway which transports proteins in an unfolded manner, the Tat pathway serves to actively translocate folded proteins across a lipid membrane bilayer. In plants, the Tat translocase is located in the thylakoid membrane of the chloroplast, where it acts to export proteins into the thylakoid lumen. In bacteria, the Tat translocase is found in the cytoplasmic membrane and serves to export proteins to the cell envelope, or to the extracellular space.

Intimin

Intimin is a virulence factor (adhesin) of EPEC and EHEC E. coli strains. It is an attaching and effacing (A/E) protein, which with other virulence factors is necessary and responsible for enteropathogenic and enterohaemorrhagic diarrhoea.

Tir is an essential component in the adherence of the enteropathogenic Escherichia coli (EPEC) and enterohemorraghic Escherichia coli (EHEC) to the cells lining the small intestine. To aid attachment, both EPEC and EHEC possess the ability to reorganise the host cell actin cytoskeleton via the secretion of virulence factors. These factors are secreted directly into the cells using a Type three secretion system. One of the virulence factors secreted is the Translocated Intimin Receptor (Tir). Tir is a receptor protein encoded by the espE gene which is located on the locus of enterocyte effacement (LEE) pathogenicity island in EPEC strains. It is secreted into the host cell membranes and acts as a receptor for intimin which is found on the bacterial surface. Once Tir binds intimin, the bacterium is attached to the enterocyte surface.

Virulence-related outer membrane protein family InterPro Family

Virulence-related outer membrane proteins are expressed in Gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion.

Fimbrial usher protein

The fimbrial usher protein is involved in biogenesis of the pilus in Gram-negative bacteria. The biogenesis of fimbriae requires a two-component assembly and transport system which is composed of a periplasmic chaperone and an outer membrane protein which has been termed a molecular 'usher'.

Trimeric autotransporter adhesin

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.

YadA bacterial adhesin protein domain

In molecular biology, YadA is a protein domain which is short for Yersinia adhesin A. These proteins have strong sequence and structural homology, particularly at their C-terminal end. The function is to promote their pathogenicity and virulence in host cells, though cell adhesion. YadA is found in three pathogenic species of Yersinia, Y. pestis,Y. pseudotuberculosis, and Y. enterocolitica. The YadA domain is encoded for by a virulence plasmid in Yersinia, which encodes a type-III secretion (T3S) system consisting of the Ysc injectisome and the Yop effectors.

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.

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport proteins 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 protein secretion machinery found in various species of Gram-negative bacteria, including various human pathogens such as Pseudomonas aeruginosa and Vibrio cholerae. The type II secretion system is one of six protein secretory systems that are commonly found in gram negative bacteria along with the type I secretion system, the type III secretion system, The type IV secretion system, 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 in gram negative bacteria.

Asparagine peptide lyase are one of the seven groups in which proteases, also termed proteolytic enzymes, peptidases, or proteinases, are classified according to their catalytic residue. The catalytic mechanism of the asparagine peptide lyases involves an asparagine residue acting as nucleophile to perform a nucleophilic elimination reaction, rather than hydrolysis, to catalyse the breaking of a peptide bond.

Bacterial secretion system

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. These major differences can be distinguished between Gram-negative and Gram-positive bacteria. But the classification is by no means clear and complete. There are at least eight types specific to Gram-negative bacteria, four to Gram-positive bacteria, while two are common to both. 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.

References

  1. Oomen CJ, van Ulsen P, van Gelder P, Feijen M, Tommassen J, Gros P (March 2004). "Structure of the translocator domain of a bacterial autotransporter". The EMBO Journal. 23 (6): 1257–66. doi:10.1038/sj.emboj.7600148. PMC   381419 Lock-green.svg. PMID   15014442.
  2. Benz I, Schmidt MA (August 2011). "Structures and functions of autotransporter proteins in microbial pathogens". International Journal of Medical Microbiology. 301 (6): 461–8. doi:10.1016/j.ijmm.2011.03.003. PMID   21616712.
  3. Pohlner J, Halter R, Beyreuther K, Meyer TF (1987). "Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease". Nature. 325 (6103): 458–62. doi:10.1038/325458a0. PMID   3027577.
  4. Leo JC, Grin I, Linke D (April 2012). "Type V secretion: mechanism(s) of autotransport through the bacterial outer membrane". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1592): 1088–101. doi:10.1098/rstb.2011.0208. PMC   3297439 Lock-green.svg. PMID   22411980.
  5. Henderson IR, Navarro-Garcia F, Nataro JP (September 1998). "The great escape: structure and function of the autotransporter proteins". Trends in Microbiology. 6 (9): 370–8. doi:10.1016/s0966-842x(98)01318-3. PMID   9778731.

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