The ATP-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans.
Sec61 or SecYEG is a membrane protein complex found in all domains of life. As the core component of the translocon, it transports proteins to the endoplasmic reticulum in eukaryotes and out of the cell in prokaryotes. It is a doughnut-shaped pore through the membrane with 3 different subunits (heterotrimeric), SecY (α), SecE (γ), and SecG (β). It has a region called the plug that blocks transport into or out of the ER. This plug is displaced when the hydrophobic region of a nascent polypeptide interacts with another region of Sec61 called the seam, allowing translocation of the polypeptide into the ER lumen.
All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that are transcribed and translated to efflux pumps. Efflux pumps are capable of moving a variety of different toxic compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters via active efflux, which is vital part for xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.
The galactose permease or GalP found in Escherichia coli is an integral membrane protein involved in the transport of monosaccharides, primarily hexoses, for utilization by E. coli in glycolysis and other metabolic and catabolic pathways (3,4). It is a member of the Major Facilitator Super Family (MFS) and is homologue of the human GLUT1 transporter (4). Below you will find descriptions of the structure, specificity, effects on homeostasis, expression, and regulation of GalP along with examples of several of its homologues.
The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABAA, GABAA-ρ, glycine, 5-HT3, and zinc-activated (ZAC) receptors. These receptors are composed of five protein subunits which form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). The name of the family refers to a characteristic loop formed by 13 highly conserved amino acids between two cysteine (Cys) residues, which form a disulfide bond near the N-terminal extracellular domain.
The Large Conductance Mechanosensitive Ion Channel (MscL) Family consists of pore-forming membrane proteins that are responsible for translating physical forces applied to cell membranes into electrophysiological activities. MscL has a relatively large conductance, 3 nS, making it permeable to ions, water, and small proteins when opened. MscL acts as stretch-activated osmotic release valve in response to osmotic shock.
General bacterial porins are a family of proteins from the outer membranes of Gram-negative bacteria. The porins act as molecular filters for hydrophilic compounds. They are responsible for the 'molecular sieve' properties of the outer membrane. Porins form large water-filled channels which allow the diffusion of hydrophilic molecules into the periplasmic space. Some porins form general diffusion channels that allow any solute up to a certain size to cross the membrane, while other porins are specific for one particular solute and contain a binding site for that solute inside the pores. As porins are the major outer membrane proteins, they also serve as receptor sites for the binding of phages and bacteriocins.
The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases are α-helical bundle primary transporters named based upon their ability to catalyze auto- (or self-) phosphorylation (hence P) of a key conserved aspartate residue within the pump and their energy source, adenosine triphosphate (ATP). In addition, they all appear to interconvert between at least two different conformations, denoted by E1 and E2. P-type ATPases fall under the P-type ATPase (P-ATPase) Superfamily (TC# 3.A.3) which, as of early 2016, includes 20 different protein families.
The SecY protein is the main transmembrane subunit of the bacterial Sec or Type II secretory pathway and a protein-secreting ATPase complex, also known as a SecYEG translocon. Homologs of the SecYEG complex are found in eukaryotes and in archaea, where the subunit is known as Sec61α.
Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). Multifunctional receptor molecules such as HKs and RTKs typically have portions on the outside of the cell that bind to hormone- or growth factor-like molecules, portions that span the cell membrane, and portions within the cell that contain the enzymatic activity. In addition to kinase activity, the intracellular domains typically have regions that bind to a secondary effector molecule or complex of molecules that further propagate signal transduction within the cell. Distinct from other classes of protein kinases, HKs are usually parts of a two-component signal transduction mechanisms in which HK transfers a phosphate group from ATP to a histidine residue within the kinase, and then to an aspartate residue on the receiver domain of a response regulator protein. More recently, the widespread existence of protein histidine phosphorylation distinct from that of two-component histidine kinases has been recognised in human cells. In marked contrast to Ser, Thr and Tyr phosphorylation, the analysis of phosphorylated Histidine using standard biochemical and mass spectrometric approaches is much more challenging, and special procedures and separation techniques are required for their preservation alongside classical Ser, Thr and Tyr phosphorylation on proteins isolated from human cells.
Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.
The Methyl-accepting chemotaxis proteins are a family of transmembrane receptors that mediate chemotactic response in certain enteric bacteria, such as Salmonella typhimurium and Escherichia coli. These methyl-accepting chemotaxis receptors are one of the first components in the sensory excitation and adaptation responses in bacteria, which act to alter swimming behaviour upon detection of specific chemicals. Use of the MCP allows bacteria to detect concentrations of molecules in the extracellular matrix so that the bacteria may smooth swim or tumble accordingly. If the bacterium detects rising levels of attractants (nutrients) or declining levels of repellents (toxins), the bacterium will continue swimming forward, or smooth swimming. If the bacterium detects declining levels of attractants or rising levels of repellents, the bacterium will tumble and re-orient itself in a new direction. In this manner, a bacterium may swim towards nutrients and away from toxins
Tripartite ATP-independent periplasmic transporters are a large family of solute transporters found in bacteria and archaea, but not in eukaryotes, that appear to be specific for the uptake of organic acids or related molecules containing a carboxylate or sulfonate group. They are unique in that they utilize a substrate binding protein (SBP) in combination with a secondary transporter.
In molecular biology, the ars operon is an operon found in several bacterial taxon. It is required for the detoxification of arsenate, arsenite, and antimonite. This system transports arsenite and antimonite out of the cell. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced glutathione (GSH) to convert arsenate to arsenite with a redox active cysteine residue in the active site. ArsC forms an active quaternary complex with GSH, arsenate, and glutaredoxin 1 (Grx1). The three ligands must be present simultaneously for reduction to occur.
EnvZ/OmpR is a two-component regulatory system widely distributed in bacteria and particularly well characterized in Escherichia coli. Its function is in osmoregulation, responding to changes in environmental osmolality by regulating the expression of the outer membrane porins OmpF and OmpC. EnvZ is a histidine kinase which also possesses a cytoplasmic osmosensory domain, and OmpR is its corresponding response regulator protein.
Many bacteria secrete small iron-binding molecules called siderophores, which bind strongly to ferric ions. FepA is an integral bacterial outer membrane porin protein that belongs to outer membrane receptor family and provides the active transport of iron bound by the siderophore enterobactin from the extracellular space, into the periplasm of Gram-negative bacteria. FepA has also been shown to transport vitamin B12, and colicins B and D as well. This protein belongs to family of ligand-gated protein channels.
SecD and SecF are prokaryotic protein export membrane proteins. They are a part of the larger multimeric protein export complex comprising SecA, D, E, F, G, Y, and YajC. SecD and SecF are required to maintain a proton motive force.
Chaperone-usher fimbriae (CU) are linear, unbranching, outer-membrane pili secreted by gram-negative bacteria through the chaperone-usher system rather than through type IV secretion or extracellular nucleation systems. These fimbriae are built up out of modular pilus subunits, which are transported into the periplasm in a Sec dependent manner. Chaperone-usher secreted fimbriae are important pathogenicity factors facilitating host colonisation, localisation and biofilm formation in clinically important species such as uropathogenic Escherichia coli and Pseudomonas aeruginosa.
Resistance-nodulation-division (RND) family transporters are a category of bacterial efflux pumps, especially identified in Gram-negative bacteria and located in the cytoplasmic membrane, that actively transport substrates. The RND superfamily includes seven families: the heavy metal efflux (HME), the hydrophobe/amphiphile efflux-1, the nodulation factor exporter family (NFE), the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family, and the hydrophobe/amphiphile efflux-3 family. These RND systems are involved in maintaining homeostasis of the cell, removal of toxic compounds, and export of virulence determinants. They have a broad substrate spectrum and can lead to the diminished activity of unrelated drug classes if over-expressed. The first reports of drug resistant bacterial infections were reported in the 1940s after the first mass production of antibiotics. Most of the RND superfamily transport systems are made of large polypeptide chains. RND proteins exist primarily in gram-negative bacteria but can also be found in gram-positive bacteria, archaea, and eukaryotes.
Proton-Translocating NAD(P)+ Transhydrogenase (E.C. 7.1.1.1) is an enzyme in that catalyzes the translocation of hydrons that are connected to the redox reaction NADH + NADP+ + H+outside => NAD+ + NADPH + H+inside
