title: Structural model of the outer vestibule and selectivity filter of the Shaker voltage-gated K+ channel.
abstract: A new generation of structural models were developed of the outer vestibule and ion-selective portion of the voltage-gated Shaker K+ channel. Some features of these models are similar to those that we have developed previously [Durrel S. R. and Guy H. R. (1992) Biophys. J. 62, 238-250; Guy H. R. (1990) In Monovalent Cations in Biological Systems (Pasternak C. A., Ed.), pp. 31-58, CRC Press, Boca Raton, FL; Guy H. R. and Durell S. R. (1994) In Molecular Evolution of Physiological processes (Fambrough D., Ed.), pp. 197-212, The Rockefeller University Press, NY; Guy H. R. and Durell S. R. (1995) In Ion Channels and Genetic Diseases (Dawson D., Ed.), pp. 1-16, The Rockefeller University Press, NY] and other features were modified to make the models more consistent with recent experimental findings. The first part of the P segment is postulated, as always, to form a short alpha helix that spans only the outer portion of the membrane. The helix is tilted so that its C-terminal is nearer the pore than its N-terminal. The latter part of the P segment, P2, is postulated to have a relatively elongated conformation that is positioned approximately parallel to the axis of the pore. Four of the P2 segments assemble to form an ion-selective region that has two narrow regions; one formed by the Y445 side-chains at the outer entrance of the pore and one formed by the backbone of the T442 residues near the innermost part of the P segments. The S6 segment is postulated to form two alpha helices. The first S6 helix packs next to the P segments in our models. The NMR structures of two scorpion toxins, charybdotoxin and agitoxin 2, have been docked into the models of the outer vestibules. The shape of the outer vestibule has been modeled so that specific toxin-channel residue-residue interactions correspond to those that have been identified experimentally.
authors.affiliation: Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5567, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Durell
authors.forename: H R
authors.initials: HR
authors.lastname: Guy
mesh_terms: D015761:4-Aminopyridine / Q000378:metabolism; D018999:Charybdotoxin; D015640:Ion Channel Gating; D008958:Models, Molecular; D009154:Mutation; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D014118:Toxins, Biological / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels; D013757:Tetraethylammonium Compounds; D014118:Toxins, Biological; C072276:kaliotoxin; D018999:Charybdotoxin; C087603:agitoxin 2; D019789:Tetraethylammonium; D015761:4-Aminopyridine