title: A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+-channels.
abstract: While S4 is known as the voltage sensor in voltage-gated potassium channels, the carboxyl terminus of S3 (S3C) is of particular interest concerning the site for gating modifier toxins like hanatoxin. The thus derived helical secondary structural arrangement for S3C, as well as its surrounding environment, has since been intensively and vigorously debated. Our previous structural analysis based on molecular simulation has provided sufficient information to describe reasonable docking conformation and further experimental designs (Lou et al., 2002. J. Mol. Recognit. 15: 175-179). However, if one only relies on such information, more advanced structure-functional interpretations for the roles S3C may play in the modification of gating behavior upon toxin binding will remain unknown. In order to have better understanding of the molecular details regarding this issue, we have performed the docking simulation with the S3C sequence from the hanatoxin-insensitive K+-channel, shaker, and analyzed the conformational changes resulting from such docking. Compared with other functional data from previous studies with respect to the proximity of the S3-S4 linker region, we suggested a significant movement of drk1 S3C, but not shaker S3C, in the direction presumably towards S4, which was comprehended as a possible factor interfering with S4 translocation during drk1 gating in the presence of toxin. In combination with the discussions for structural roles of the length of the S3-S4 linker, a possible molecular mechanism to illustrate the hanatoxin binding-modified gating is proposed.
authors.affiliation: Graduate Institute of Oral Biology, Medical College, National Taiwan University, Taipei, Taiwan, Republic of China. kllou@ntumc.org
authors.forename: Kuo-Long
authors.initials: KL
authors.lastname: Lou
authors.forename: Po-Tsang
authors.initials: PT
authors.lastname: Huang
authors.forename: Yu-Shuan
authors.initials: YS
authors.lastname: Shiau
authors.forename: Yen-Chywan
authors.initials: YC
authors.lastname: Liaw
authors.forename: Yuh-Yuan
authors.initials: YY
authors.lastname: Shiau
authors.forename: Horng-Huei
authors.initials: HH
authors.lastname: Liou
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels; D049692:History, Early Modern 1451-1600; D015640:Ion Channel Gating; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels
chemical_list: D051668:Delayed Rectifier Potassium Channels; D010455:Peptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels; C096469:hanatoxin