Pore-forming proteins

Colicins are pore-forming proteins, produced by certain strains of E. coli, that kill or inhibit the growth of other, competing bacteria and even other strains of E. coli (a process known as allelopathy). Channel-forming colicins are released as soluble monomers. Upon encountering a host cell, the colicin molecule traverses the bacterial outer membrane and periplasm, then inserts itself... 

In reconstitution experiments, the self-assembly of the pore-forming protein a-hemolysin of Staphylococcus aureus (aHL) [181-183] was examined in plain and S-layer-supported lipid bilayers. Staphylococcal aHL formed lytic pores when added to the lipid-exposed side of the DPhPC bilayer with or without an attached S-layer from B coagulans E38/vl. The assembly of aHL pores was slower at S-layer-supported compared to unsupported folded membranes. No assembly could be detected upon adding aHL monomers to the S-layer face of the composite membrane. Therefore, the intrinsic molecular sieving properties of the S-layer lattice did not allow passage of aHL monomers through the S-layer pores to the lipid bilayer [142]. 

The transmembrane potential of cardiac cells is determined by the concentrations of several ions—chiefly sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl-)—on either side of the membrane and the permeability of the membrane to each ion. These water-soluble ions are unable to freely diffuse across the lipid cell membrane in response to their electrical and concentration gradients they require aqueous channels (specific pore-forming proteins) for such diffusion. Thus, ions move across cell membranes in response to their gradients only at specific times during the cardiac cycle when these ion channels are open. The movements of the ions produce currents that form the basis of the cardiac action potential. Individual channels are relatively ion-specific, and the flux of ions through them is... 

Bacterial pore-forming proteins, such as oc-hemolysin, secreted by Staphylococcus aureus can be modified so that pore formation is activated by chemical, biochemical, or physical triggers. Such hemolysins, when targeted to tumors, could increase tumor permeability, and hence susceptibility to various cytotoxic drugs (78). 

The most abundant protein in the E. coli outer membrane is OmpA. It appears to form a transmembrane helical bundle. Although it is regarded primarily as a structural protein it too acts, in monomeric form, as an inefficient diffusion pore.350 Mitochondrial outer membranes contain nonspecific pores (mitochondrial porins) that allow passage of sucrose and other saccharides of molecular mass up to 2 to 8 kDa.351 352 Similar pore-forming proteins have been found in plant peroxisomes.353... 

Natural killer (NK) cells Destroy infected and malignant cells with pore-forming protein perforin and cytotoxic granules... 

The interactions of several peptides with phospholipids have been studied by computer simulation. Emphasis has been given to several aspects of protein-phospholipid interactions, including the way of association and orientational preference of peptides in contact with a bilayer, the effect of phospholipids on the preference and stability of helical conformations, and the effect of the inserted peptide on the structure and dynamics of the phospholipids. These investigations have been extended to bundles of helices and even whole pore-forming proteins. In particular, the simulation of ion channels and of peptides with antimicrobial action has attracted a great deal of attention in theoretical studies. 

Figure 1.3. Diagram of cell membrane. The plasma membrane is a lipid bilayer containing peripheral proteins, including HLA antigens, proteoglycans, and integral proteins, such as pore-forming proteins that transverse the cell membrane.

Gu, L. Q., Braha, O., Conlan, S., Cheley, S., and Bayley, H. (1999). Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature 398, 686-690. 

At very high concentration, will trigger apoptosis (progranuned cell death) in many cells. Thus, if a cell is rendered permeable to calcium by some pore-forming protein, it will commit suicide - a principle widely used by the immune system (complement, perform), as well as microbes, which frequently secrete pore-forming protein toxins. 

One of the best-studied examples of protein incorporation is the mitochondrial outer membrane. In yeast and Neurospora crassa none of the outer membrane proteins studied thus far are made as larger precursors. All of these proteins are made on free ribosomes and are incorporated into the outer membrane post-translationally [35,69,99]. The import of the porin (a pore-forming protein) is time and temperature dependent but does not require energy [35,99]. The incorporation of porin in vitro was found to be membrane specific [35]. How is this membrane specificity determined, and what anchors the outer membrane protein to the outer membrane ... 

Bayley H (1994) Triggers and switches in self-assembling pore-forming proteins. In J Cell Biochem 56 177-182. 

Chang C, Niblack B, Walker B et al. (1995) A photogenerated pore-forming protein. In Chemistry Biology 2 391 -400. 

Walker B, Bayley H (1994) A pore-forming protein with a protease-activated trigger. In Protein Engineering 7 91-97. 

Walker B, Braha O, Cheley S et al. (1995) An intermediate in the assembly of a pore-forming protein trapped with a genetically-engineered switch. In Chemistry Biology 99-105. 

The outer membrane is quite permeable to most small molecules and ions because it contains many copies of mitochondrial porin, a 30 to. iSkd pore-forming protein also known as VDAC, tor voltage-dependent anion channel. VDAC plays a role in the regulated flux of metabolites—... 

Cyclic peptides as molecular adaptors for a pore-forming protein, J. Sanchez-Quesada, M. R. Ghadiri, H. Bayley and O. Braha, J. Am. Chem. Soc., 2000, 122, 11757. 

Natural killer (NK) cells and cytotoxic T lymphocytes (CTL) are the primary line of defense against viruses and other intracellular pathogens in the immune system. The cytotoxic lymphocytes recognize infected host cells and kill them with the help of the pore-forming protein perforin and by proteolytic events carried out by members of the granzyme family of serine proteases. Although an essential component of immunity under normal conditions, aberrant cytotoxic lymphocyte activity has been associated with autoimmune disorders such as rheumatoid arthritis, diabetes, or allograft rejection [65],... 

The Torpedo AChR, a muscle-type AChR, is a pentameric protein whereas the T4M28 pore-forming protein described is a four-helix bundle. The five-helix bundle (T5M28) has not yet been characterized therefore, a detailed comparison of the single-channel conductance of Torpedo AChR with a T5M28 is not possible. However, information about the channel properties of other members of the superfamily of nicotinic AChRs is available. 

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