Pore-forming domain

The N-terminal portion of the 522-residue polypeptide chain of colicin El appears to be required for transport into the membrane and the central part for binding to the receptor the channelforming property is characteristic of the C-terminal region.k A similar organization has been established for the smaller colicin N translocation domain, (residues 1-66), receptor domain, (residues 67-182), and pore-forming domain (residues 183-387). 

Once internalized, the essential step for the polyplex is to escape rapidly the endosomal vesicle in order to release the nucleic acid in the cytosol and prevent its lysosomal degradation. As the endosomal and lysosomal pH presents values between 4.5 and 6.5 and therefore differs from the neutral pH of 7.4 in other biological compartments [58], some polycations containing protonable residues like PEI facilitate this step by the proton sponge effect [59, 60]. As not all cationic polymers display this attribute, another effective method for enhanced endosomal polyplex release is incorporation of specific endosomal membrane disrupting or pore-forming domains, such as lytic lipid moieties or endosomolytic peptides. 

A recent structure-based lead-finding strategy was used for Kvl.5 inhibitors. The pore-forming domain of Kvl. 5 exhibits 54% sequence homology with the bacterial K+ channel KcsA from Streptomyces lividans, for which a crystal structure of the... 

A salient feature of all known pores is their irreversible anchorage in the lipid bilayer (Bhakdi and Tranum-Jensen, 1987). Hence, membrane-bound PFTs must be amphiphilic, possessing a lipid binding surface and a hydrophilic face that lines the aqueous channel. The pore-forming domains themselves are unlikely to harbor extended stretches of hydrophobic amino acid residues. Rather, they would be expected to possess amphipathic secondary structure. Rules to identify or predict pore-forming sequences do not exist, and even the solution of the structure of a water-soluble protomer form will not permit conclusions to be drawn on the structure of the pore. This situation is given in the case of aerolysin (Parker et al., 1996). 

Vos JC, Reits EA, Wojcik-Jacobs E, NeeQes J (1999b) Head-head/tail-tail relative orientation of the pore-forming domains of the heterodimeric ABC transporter TAP. Curr Biol 10 1-7 Watts C (1997) Capture and processing of exogenous antigens for presentation on MHC molecules. Annu Rev Immunol 15 821-50... 

After insertion of the Cry 8-endotoxin, several receptor-toxin complexes then form aggregates that form pores in the membrane (Walters et al., 1993 Knowles, 1994 Soberon et al., 2000). The pores formed in the plasma membrane disrupt the osmotic balance within the cells which causes the cells to swell and burst. At this point, the insects stop feeding. Domain I in Cry proteins was shown to be a pore forming domain (Walters et al., 1993 VonTersch et al., 1994). The left-handed supercoil of domain I, made up of a-helices, is clearly equipped for membrane insertion (Li, 1996). Furthermore,... 

Gerber, D. and Y. Shai. 2000. Insertion and organization within membranes of the 8-endotoxin pore-forming domain, helix 4-loop-helix 5, and inhibition of its activity by a mutant helix 4 peptide. J. Biol. Chem. 275 23602-23607. 

Sobolevsky Al, Prodromou ML, Yelshansky MV, WoUmuth LP (2007) Subunit-specific contribution of pore-forming domains to NMDA receptor channel structure and gating. J Gen Physiol... 

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