TCDB is operated by the Saier Lab Bioinformatics Group
1: Channels/Pores

Channel-type facilitators. Proteins in this category have transmembrane channels which consist largely of α-helical or β-strand-type spanners. Transport systems of this type catalyze facilitated diffusion (by an energy-independent process) by passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism. They do not exhibit stereospecificity but may be specific for a particular molecular species or class of molecules.

These include:

1.A. α-Type Channels. Transmembrane channel proteins of this class are ubiquitously found in the membranes of all types of organisms from bacteria to higher eukaryotes. These transporters usually catalyze movement of solutes by an energy-independent process by passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism. These channel proteins usually consist largely of α-helical spanners, although β-strands may be present and may even contribute to the channel. Outer membrane porin-type channel proteins are excluded from this class and are instead included in class 1.B.

1.B. β-Barrel Porins. These proteins form transmembrane pores that usually allow the energy independent passage of solutes across a membrane. The transmembrane portions of these proteins consist exclusively of β-strands which form a β-barrel. These porin-type proteins are found in the outer membranes of Gram-negative bacteria, mitochondria, plastids and possibly acid-fast Gram-positive bacteria.

1.C. Pore-Forming Toxins. These proteins/peptides are synthesized by one cell and secreted for insertion into the membrane of another cell where they form transmembrane pores. They may exert their toxic effects by allowing the free flow of electrolytes and other small molecules across the membrane, or they may allow entry into the target cell cytoplasm of a toxin protein that ultimately kills the cell. Both protein (large) and ribosomally synthesized peptide (small) toxins are included in this category.

1.D. Non-Ribosomally Synthesized Channels. These molecules, often chains of L- and D-amino acids as well as other small molecular building blocks such as hydroxy acids (i.e., lactate), form oligomeric transmembrane ion channels. Voltage may induce channel formation by promoting assembly of the oligomeric transmembrane pore-forming structure. These depsipeptides are often made by bacteria and fungi as agents of biological warfare. Other substances, completely lacking amino acids, are also capable of channel-formation.

1.E. Holins. Holins consist of about forty distinct families of proteins that exhibit common structural and functional characteristics but which do not exhibit statistically significant sequence similarity between members of distinct families. They are encoded within the genomes of Gram-positive and Gram-negative bacteria as well as those of the bacteriophage of these organisms. Their primary function appears to be transport of murein hydrolases across the cytoplasmic membrane to the cell wall where these enzymes hydrolyze the cell wall polymer as a prelude to cell lysis. When chromosomally encoded, these enzymes are therefore autolysins. Holins may also facilitate leakage of electrolytes and nutrients from the cell cytoplasm, thereby promoting cell death. Some may catalyze export of nucleases.

1.F. Vesicle Fusion Pores. Many substances (neurotransmitters, protein, complex carbohydrates, small molecules such as ATP) in eukaryotes are sequestered in vesicles which then fuse with the plasma membrane releasing to the extracellular medium the intra-vesicular contents. The vesicles can then either reform or remain associated with the plasma membrane. In the latter case, the lipids flow from the vesicle into the plasma membrane. Recently, fusion has been shown to initiate by formation of a pore complex of various pore sizes.

1.G. Viral Fusion Pores. Three distinct classes of viral membrane fusion proteins have been identified based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins.

1.H. Paracellular Channels. Paracellular transport occurs across intercellular tight junctions of epithelia and is important for reabsorption of ions, drugs and nutrients, particularly in the kidney. Paracellular transport is passive. It occurs outside of cells following concentration gradients and transcellular electrical potentials.

1.I. Membrane-bounded Channels. Membrane-bounded channels allow passage of molecules across cell or organelle membranes. For example, the Nuclear Pore Complex (NPC; 1.I.1) allows the flow of small molecules and macromolecules between the nucleus and the cytoplasm. The Plant Plasmodesmata (PPD; 1.I.2) allows the flow of similar molecules between adjacent plant cells. Both are complex with many protein constituents.

1.J. Virion Egress Pyramidal Apertures. Some archaeal viruses use an egress mechanism involving virus-associated pyramids (VAPs) on the host cell surface. At the end of the infection cycle, these structures open outward and create apertures through which mature virions escape from the cell.

1.K. Phage DNA Injection Channels. A representative phage DNA injection channel is the contractile tail complex of phage T4 with a tail tube that traverses the bacterial outer membrane creating a channel for delivery of the viral genome.

1.L. Tunneling Nanotubes, TNTs. TNTs connect adjacent cells of the immune system such as lymphocytes, allowing transfer of proteins, small cytoplasmic molecules and membrane constituents between the interconnected cells.

1.M: Membrane Fusion-mediating Spanins. Spanins span the inner and outer membrane of Gram-negaive bacteria and facilitate cell lysis together with holins (TC subclass 1.E) and autolysins.  They may facilitate fusion of the inner and outer membranes. 

1.N: Cell Fusion Pores. Several distinct systems mediate fusion of membranes both between cells and within cells. These include:  1) osteoclasts, 2) myoblasts, 3) gametes, 4) multiple cell types, 5) endoplasmic membranes and 6) the mitochondrial inner and out membranes.

1.O: Physical Force (Sonoporation/Electroporation)-induced Pores. Several physical forces and induced pore-formation followed by resealing of the pores without killing the cell.  Prominent of these are electroporation and sonoporation, but applied voltages can accomplish pore formation.