Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in TMDs are often hydrophobic, although proteins such as membrane pumps and ion channels can contain polar residues. TMDs vary greatly in size and hydrophobicity; they may adopt organelle-specific properties.
Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane and can either penetrate the membrane (transmembrane) or associate with one or the other side of a membrane. Peripheral membrane proteins are transiently associated with the cell membrane.
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. 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. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents.
Topology of a transmembrane protein refers to locations of N- and C-termini of membrane-spanning polypeptide chain with respect to the inner or outer sides of the biological membrane occupied by the protein.
Mycobacterium is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy in humans. The Greek prefix myco- means 'fungus', alluding to this genus' mold-like colony surfaces. Since this genus has cell walls with a waxy lipid-rich outer layer that contains high concentrations of mycolic acid, acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.
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. 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.
The cell envelope comprises the inner cell membrane and the cell wall of a bacterium. In gram-negative bacteria an outer membrane is also included. This envelope is not present in the Mollicutes where the cell wall is absent.
Nanopore sequencing is a third generation approach used in the sequencing of biopolymers — specifically, polynucleotides in the form of DNA or RNA.
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.
The Transporter Classification Database is an International Union of Biochemistry and Molecular Biology (IUBMB)-approved classification system for membrane transport proteins, including ion channels.
In protein structures, a beta barrel is a beta sheet composed of tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand. Beta-strands in many beta-barrels are arranged in an antiparallel fashion. Beta barrel structures are named for resemblance to the barrels used to contain liquids. Most of them are water-soluble proteins and frequently bind hydrophobic ligands in the barrel center, as in lipocalins. Others span cell membranes and are commonly found in porins. Porin-like barrel structures are encoded by as many as 2–3% of the genes in Gram-negative bacteria. It has been shown that more than 600 proteins with various function contain the beta barrel structure.
Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered.
Voltage-dependent anion channels, or mitochondrial porins, are a class of porin ion channel located on the outer mitochondrial membrane. There is debate as to whether or not this channel is expressed in the cell surface membrane.
General bacterial porins are a family of porin 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.
Outer membrane receptors, also known as TonB-dependent receptors, are a family of beta barrel proteins named for their localization in the outer membrane of gram-negative bacteria. TonB complexes sense signals from the outside of bacterial cells and transmit them into the cytoplasm, leading to transcriptional activation of target genes. TonB-dependent receptors in gram-negative bacteria are associated with the uptake and transport of large substrates such as iron siderophore complexes and vitamin B12.
Maltoporins are bacterial outer membrane proteins of the porin family. Maltoporin forms a trimeric structure which facilitates the diffusion of maltodextrins across the outer membrane of Gram-negative bacteria. The membrane channel is formed by an antiparallel beta-barrel.
In molecular biology, the OmpA domain is a conserved protein domain with a beta/alpha/beta/alpha-beta(2) structure found in the C-terminal region of many Gram-negative bacterial outer membrane proteins, such as porin-like integral membrane proteins, small lipid-anchored proteins, and MotB proton channels. The N-terminal half of these proteins is variable although some of the proteins in this group have the OmpA-like transmembrane domain at the N terminus. OmpA from Escherichia coli is required for pathogenesis, and can interact with host receptor molecules. MotB serve two functions in E. coli, the MotA(4)-MotB(2) complex attaches to the cell wall via MotB to form the stator of the flagellar motor, and the MotA-MotB complex couples the flow of ions across the cell membrane to movement of the rotor.
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.
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.
