Pore domain

This family of K+ channels, with >50 distinct gene members, typically contains four putative transmembrane and two pore domains. The G(Y/F)G motif is... 

SI— S4 forms the voltage-sensing domain, while S5—S6 forms the pore domain of the channel. The majority of drugs that directly modify hERG function bind to the channel pore. Between S5 and S6 is a peptide loop that contains the pore helix and the selectivity filter. N- and C-terminal domains are on the cytoplasmic side of the... 

In vivo studies employing tests of acute pain unequivocally showed the involvement of Katp, Kv1.1 and Ca2+-activated K+ channels in supraspinal, spinal and peripheral analgesia produced by different classes of analgesics. Furthermore, two-pore-domain and G-protein gated inward rectifier (Kir3.x) K+ channels are affected by volatile anesthetics. The latter also contribute to p- and K-opioid receptor-mediated analgesia (Ikeda et al., 2000). 

Patel, A. J., Honore, E., Lesage, F., Fink, M., Romey, G., Lazdunski, M. Inhalational anesthetics activate two-pore-domain background iC channels, Nature Neuroscience 1999, 2, 422-426. 

Sirois, J. E., Lei, Q., Talley, E. M., Lynch III, C., Bayliss, D. A. The TASK-1 two-pore domain fC channel is a molecular substrate for neuronal effects of inhalational anesthetics, The Journal of Neuroscience 2000, 20, 6347-6354. 

The DTG curves for uncalcined HR-B2 and B3 still exhibited some similarity to those of good-quality samples, such as HR-A1 - A3, but resemble more closely the DTG curve for an uncalcined lamellar phase [22], XRD revealed the presence of hexagonally ordered domains in the calcined HR-B2 and B3 samples, whereas adsorption data showed the presence of ordered pore domains of the size in accord with the XRD interplanar spacing (see Table 2). 

Maingret F., Patel A. J., Lesage F., Lazdunski M., and Honore E. (2000). Lysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. J. Biol. Chem. 275 10128-10133. 

Figure 8.4 Structure of potassium channels with different binding sites in the pore domain marked. To show the binding location of R-L3 between helices S5 and S6, only the monomer is shown.

The Streptomyces lividans K+ channel (KcsA) is a 160-residue protein that forms homotetrameric channels closely related to the pore domain of larger voltage-dependent channels (Schrempf et al., 1995). When purified and reconstituted in lipid bilayers, KcsA catalyzes single-channel activities with selectivity properties identical to those of other eukaryotic K+ channels (Cuello et al., 1998 Heginbotham et al., 1999 Meuser et al., 1999). The fact that KcsA is easily expressed in Escherichia coli at milligram levels made this protein an ideal target for structural analysis. 

Tikhonov, D. B., Mellor, J. R., Usherwood, P. N., and Magazanik, L. G. (2002). Modeling of the pore domain of the GLURl channel Homology with channel and binding of channel blockers. Biophys. J. 82, 1884-1893. 

Owen P. Hamill, ed. Mechanosensitive Ion Channels, Current Topics in Membranes Part A, vol. 58. 2007. Elsevier Inc., New York. pp. 1-424. http //www.sciencedirect.com/science/bookseries/I0635823. Owen P. Hamill, ed. Mechanosensitive Ion Channels, Current Topics in Membranes Part B, vol. 59. 2007. Elsevier Inc., New York. pp. 1-588. http //www.sciencedirect.com/science/bookseries/10635823. Patel AJ, Honord E, Lesage F, Fink M, Romey G, Lazdunski M. Inhalational anesthetics activate two-pore-domain background K+ channels. Nat. Neurosci. 1999 2 422-426. 

Sour taste detects acids, i.e., protons. Several different sour taste receptor candidates such as acid-sensing ion channels (ASICs) (57), hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) (58), and two pore domain potassium channels (K2PS) (59, 60) have been described in the past. In addition, recent research identified two members of the polycystic kidney disease (PKD) family of the transient receptor potential superfamily (TRP) as strong sour taste receptor candidates or as part thereof. Immunohistochemistry and in situ hybridization revealed the presence of the polycystic-kidney-disease-like ion channel PKD2L1 in subsets of taste receptor cells of mouse fungiform, vallate, and foliate papillae. These cells differ from... 

Richter TA, Dvoryanchikov GA, Chaudhari N, Roper SD. Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds. J. Neurophysiol. 2004 92 1928-1936. 

Z.R. Zhang, S.I. McDonough, and N.A. McCarty. 2000. Interaction between permeation and gating in the putative pore domain mutant in the cystic fibrosis transmembrane conductance regulator P/o/ /ryv. J. 79 298-313. (PubMed)... 

A total of four subunits are required to form a functional channel, with the pore domains associating with one another to form a symmetrical tetrameric construct, encasing a conduction pore. The highly conserved pore helix and selectivity filter are critical to the selective and rapid throughput of K+ ions [96], These features appear as if mounted on the S5 and S6 transmembrane helices and constitute the extracellular portion of the membrane pore [97], The intracellular portion of the pore is predominantly lined by the S6 helix to create an aqueous cavity below the selectivity filter [97], It is to this site that compounds bind to prevent K+ ion conduction [87,98],... 

In addition to the pore domain, it is possible to create homology models of the voltage-sensor and C-terminal domains of hERG. There are also two structures of hERG itself, a crystal structure of the Per-Arnt-Sim (PAS) domain, found within the N-terminus [112], and an NMR solution structure of the S5 to pore helix linker (Turret) [113]. A full list of crystal structures that can be used to create homology models of hERG is shown in Table 16.2. 

In cases such as KcsA, where there are many PDB entries for the same general structure, an example PDB ID is given. The Turret is not a domain per se, rather an extracellular loop between S5 and the pore helix of the pore domain. 

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