General bacterial porin family

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Gram-negative porin
1pho opm.png
Identifiers
SymbolPorin_1
Pfam PF00267
Pfam clan CL0193
InterPro IPR001702
PROSITE PDOC00498
SCOP2 1mpf / SCOPe / SUPFAM
TCDB 1.B.1
OPM superfamily 31
OPM protein 1pho
CDD cd01345

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. [1] 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 (that size is known as the exclusion limit) to cross the membrane, while other porins are specific for one particular solute and contain a binding site for that solute inside the pores (these are known as selective porins). As porins are the major outer membrane proteins, they also serve as receptor sites for the binding of phages and bacteriocins.

Contents

General diffusion porins usually assemble as a trimer in the membrane, and the transmembrane core of these proteins is composed exclusively of beta strands. [2] It has been shown [3] that a number of porins are evolutionarily related.

Structure of Porins

MlaA lipoprotein
Identifiers
SymbolMlaA
Pfam PF04333
OPM superfamily 31
OPM protein 5nup

Porins are composed of β-strands, which are, in general, linked together by beta turns on the periplasmic side of the outer membrane and long loops on the external side of the membrane. The β strands lie in an antiparallel fashion and form a cylindrical tube, called a β-barrel[2]. The amino acid composition of the porin β-strands are unique in that polar and non-polar residues alternate along them. This means that the non-polar residues face outwards so as to interact with the non-polar lipid membrane, whereas the polar residues face inwards into the center of the β-barrel to form the aqueous channel. The phospholipids that comprise the outer membrane give it the same semi-permeable characteristics as the cytoplasmic membrane [4]

The porin channel is partially blocked by a loop, called the eyelet, which projects into the cavity. In general, it is found between strands 5 and 6 of each barrel, and it defines the size of solute that can traverse the channel. It is lined almost exclusively with charged amino acyl residues arranged on opposite sides of the channel, creating a transversal electric field across the pore. The eyelet has a local surplus of negative charges from four glutamic acid and seven aspartic acid residues (in contrast to one histidine, two lysine and three arginine residues) is partially compensated for by two bound calcium atoms, and this asymmetric arrangement of molecules is thought to have an influence in the selection of molecules that can pass through the channel[3].

Some osmoporins, such as OmpC, forms a complex with alpha-helical transmembrane protein MlaA to maintain outer membrane lipid asymmetry. [5]

Homologous Families

Three dimensional structural analyses show that there are many (at-least 48) other families which share sufficient sequence similarity to the General Bacterial Porin(GBP) family. are homologous in structure and function to General bacterial porin family. One such family is The Sugar Porin (SP) Family. (TC# 1.B.3) The SP family includes the well characterized maltoporin of E. coli for which the three-dimensional structures with and without its substrate have been obtained by X-ray diffraction. The protein consists of an 18 β-stranded β-barrel in contrast to proteins of the general bacterial porin family (GBP) and the Rhodobacter PorCa Porin (RPP) family(TC# 1.B.7)) which consist of 16 β-stranded β-barrels. Although maltoporin contains a wider beta-barrel than the porins of the GBP (TC# 1.B.1) and RPP families(TC# 1.B.7), it exhibits a narrower channel, showing only 5% of the ionic conductance of the latter porins.

The Rhodobacter PorCa Protein, the only well characterized member of the RPP family, was the first porin to yield its three-dimensional structure by X-ray crystallography. It has a 16-stranded β-barrel structure similar to that of the members of the GBP (TC #1.B.1) family. Paupit et al. (1991) presented crystal structures of phosphoporin (PhoE; TC# 1.B.1.1.2), maltoporin (LamB; TC# 1.B.3.1.1) and Matrixporin (OmpF), all of E. coli, and found these have 3-d folds similar to that of the Rhodobacter porin, PorCa. Structural and sequence analysis provide firm evidence that the GBP, SP and RPP families together with 44 additional families in TCDB belong to a single superfamily. However, we have been able to demonstrate homology between members of families GBP and RPP using statistical means (M. Saier, unpublished results).

Porin Superfamilies

General bacterial porin family belongs to Porin Superfamily I. The homologous families Sugar Porin(SP) family and Rhodobacter PorCa Porin (RPP) Family also belong to the Porin Superfamily I.

Subfamilies

Related Research Articles

A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. 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 length, sequence, and hydrophobicity, adopting organelle-specific properties.

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. 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.

A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion or active transport. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.

Porin (protein) Group of transport proteins

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.

Beta barrel

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.

Anthrax toxin Tripartite protein complex secreted by virulent strains of Bacillus anthracis

Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes.

Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named hemolysins, and so on. Cytolysins may be involved in immunity as well as in venoms.

Mitochondrial membrane transport protein

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 channel Class of porin ion channels in the outer mitochondrial membrane

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.

OmpA-like transmembrane domain

OmpA-like transmembrane domain is an evolutionarily conserved domain of bacterial outer membrane proteins. This domain consists of an eight-stranded beta barrel. OmpA is the predominant cell surface antigen in enterobacteria found in about 100,000 copies per cell. The expression of OmpA is tightly regulated by a variety of mechanisms. One mechanism by which OmpA expression is regulated in Vibrio species is by an antisense non-coding RNA called VrrA.

Maltoporin

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.

Virulence-related outer membrane protein family

Virulence-related outer membrane proteins, or outer surface proteins (Osp) in some contexts, are expressed in the outer membrane of gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion.

Major intrinsic proteins

Major intrinsic proteins comprise a large superfamily of transmembrane protein channels that are grouped together on the basis of homology. The MIP superfamily includes three subfamilies: aquaporins, aquaglyceroporins and S-aquaporins.

  1. The aquaporins (AQPs) are water selective.
  2. The aquaglyceroporins are permeable to water, but also to other small uncharged molecules such as glycerol.
  3. The third subfamily, with little conserved amino acid sequences around the NPA boxes, include 'superaquaporins' (S-aquaporins).
VDAC1 Protein-coding gene in the species Homo sapiens

Voltage-dependent anion-selective channel 1 (VDAC-1) is a beta barrel protein that in humans is encoded by the VDAC1 gene located on chromosome 5. It forms an ion channel in the outer mitochondrial membrane (OMM) and also the outer cell membrane. In the OMM, it allows ATP to diffuse out of the mitochondria into the cytoplasm. In the cell membrane, it is involved in volume regulation. Within all eukaryotic cells, mitochondria are responsible for synthesis of ATP among other metabolite needed for cell survival. VDAC1 therefore allows for communication between the mitochondrion and the cell mediating the balance between cell metabolism and cell death. Besides metabolic permeation, VDAC1 also acts as a scaffold for proteins such as hexokinase that can in turn regulate metabolism.

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.

The thiol-activated Cholesterol-dependent Cytolysin(CDC) family is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 monomers. Through multiple conformational changes, the β-barrel transmembrane structure is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore formation, though the presence of cholesterol is not required by all CDCs for binding. For example, intermedilysin secreted by Streptococcus intermedius will bind only to target membranes containing a specific protein receptor, independent of the presence of cholesterol, but cholesterol is required by intermedilysin for pore formation. While the lipid environment of cholesterol in the membrane can affect toxin binding, the exact molecular mechanism that cholesterol regulates the cytolytic activity of the CDC is not fully understood.

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.

OmpA domain

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.

OmpT

OmpT is an aspartyl protease found on the outer membrane of Escherichia coli. OmpT is a subtype of the family of omptin proteases, which are found on some gram-negative species of bacteria.

References

  1. Benz R, Bauer K (1988). "Permeation of hydrophilic molecules through the outer membrane of gram-negative bacteria. Review on bacterial porins". Eur. J. Biochem. 176 (1): 1–19. doi: 10.1111/j.1432-1033.1988.tb14245.x . PMID   2901351.
  2. Jap BK, Walian PJ (1990). "Biophysics of the structure and function of porins". Q. Rev. Biophys. 23 (4): 367–403. doi:10.1017/S003358350000559X. PMID   2178269.
  3. Pattus F, Jeanteur D, Lakey JH (1991). "The bacterial porin superfamily: sequence alignment and structure prediction". Mol. Microbiol. 5 (9): 2153–2164. doi:10.1111/j.1365-2958.1991.tb02145.x. PMID   1662760. S2CID   29688606.
  4. Van Gelder P, Saint N, van Boxtel R, Rosenbusch JP, Tommassen J (1997). "Pore functioning of outer membrane protein PhoE of Escherichia col". Protein Eng. 10 (6): 699–706. doi: 10.1093/protein/10.6.699 . PMID   9278284.
  5. Chong, Zhi-Soon; Woo, Wei-Fen; Chng, Shu-Sin (2015-12-01). "Osmoporin OmpC forms a complex with MlaA to maintain outer membrane lipid asymmetry in Escherichia coli". Molecular Microbiology. 98 (6): 1133–1146. doi: 10.1111/mmi.13202 . ISSN   1365-2958. PMID   26314242.