Channel-forming domain

Colicin El is a 522-residue polypeptide ich is lethal to strains of E. coti that do not contain the re tance plasmid. Colicin El exeits its toxic effects by forming a channel in the cyto 4asmic metribrane which depolarizes and deenergizes the cell. The active channel forming domain consists... 

D. Huster, L. Xiao, M. Hong, Sohd-state NMR investigation of the dynamics of the soluble and membrane-bound colicin la channel-forming domain. Biochemistry 40 (2001) 7662-7674. 

Hvomp, R.N. and Saier, M.H., Jr. (2002) Sequence similarity between the channel-forming domains of voltage-gated ion channel proteins and the C-terminal domains of secondary carriers of the major facilitator superfamily. Microbiology 148,3760-3762. 

In cyclic nucleotide-regulated channels, this domain serves as a high-affinity binding site for 3-5 cyclic monophosphates. The CNBD of channels has a significant sequence similarity to the CNBD of most other classes of eukaryotic cyclic nucleotide receptors and to the CNBD of the prokaryotic catabolite activator protein (CAP). The primary sequence of CNBDs consists of approximately 120 amino acid residues forming three a-helices (oA-aC) and eight (3-strands ( 31- 38). 

For nearly symmetric compositions the unlike blocks form domains composed of alternating layers, known as lamellar phase (L). Slightly off-symmetry composition results in the formation of a different layered structure. The structure is known as perforated layers (PI) or catenoid phase. Despite an earlier assignment as an equilibrium phase, it is now known to be in a long-lived metastable state that facilitates the transition from I to G phases [9-14], The PL structure consists of alternating minority and majority component layers in which hexagonally packed channels of the majority component extend through the minority component. 

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... 

Park SH, Mrse AA, Nevzorov AA, Mesleh MF, Oblatt-Montal M, Montal M, Opella SJ. Three-dimensional structure of the channel-forming trans-membrane domain of virus protein u (Vpu) from HIV-L J. Mol. Biol. 2003 333 409-424. 

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). 

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