| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Virginia Commonwealth University, Richmond, VA 23298, USA
2 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia
The hERG channel has an unusually long ‘S5–P linker’ (residues 571–613) that lines the outer mouth of the pore. Previously, we have shown that residues along this S5–P linker are critical for the fast-inactivation process and K+ selectivity of the hERG channel. Here we used several approaches to probe the structure of this S5–P linker and its interactions with other domains of the hERG channel. Circular dichroism and NMR analysis of a synthetic hERG S5–P linker peptide suggested that this linker is quite dynamic: its central region (positions 583–593) can be unstructured or helical, depending on whether it is immersed in an aqueous phase or in contact with a hydrophobic environment. Cysteine introduced into positions 583–597 of the S5–P linker can form intersubunit disulphide bonds, and at least four of them (at 584, 585, 588 and 589) can form disulphide bonds with counterparts from neighbouring subunits. We propose that the four S5–P linkers in a hERG channel can engage in dynamic conformational changes during channel gating, and interactions between S5–P linkers from neighbouring subunits contribute importantly to channel inactivation.
(Received 27 June 2005;
accepted after revision 2 September 2005;
first published online 8 September 2005)
Corresponding author G.-N. Tseng: Department of Physiology, Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298, USA. Email: gtseng{at}hsc.vcu.edu
This article has been cited by other articles:
|
|
 |
|
  X. Xu, M. Recanatini, M. Roberti, and G.-N. Tseng Probing the Binding Sites and Mechanisms of Action of Two Human Ether-a-go-go-Related Gene Channel Activators, 1,3-bis-(2-Hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and 2-[2-(3,4-Dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD307243) Mol. Pharmacol., June 1, 2008; 73(6): 1709 - 1721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gordon, I. M. Lozinskaya, Z. Lin, S. F. Semus, F. E. Blaney, R. N. Willette, and X. Xu 2-[2-(3,4-Dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic Acid (PD-307243) Causes Instantaneous Current through Human Ether-a-go-go-Related Gene Potassium Channels Mol. Pharmacol., March 1, 2008; 73(3): 639 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhang, X.-S. Liu, S. Diochot, M. Lazdunski, and G.-N. Tseng APETx1 from Sea Anemone Anthopleura elegantissima Is a Gating Modifier Peptide Toxin of the Human Ether-a-go-go- Related Potassium Channel Mol. Pharmacol., August 1, 2007; 72(2): 259 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Hill, M. Sunde, T. J. Campbell, and J. I. Vandenberg Mechanism of Block of the hERG K+ Channel by the Scorpion Toxin CnErg1 Biophys. J., June 1, 2007; 92(11): 3915 - 3929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-N. Tseng, K. D. Sonawane, Y. V. Korolkova, M. Zhang, J. Liu, E. V. Grishin, and H. R. Guy Probing the Outer Mouth Structure of the hERG Channel with Peptide Toxin Footprinting and Molecular Modeling Biophys. J., May 15, 2007; 92(10): 3524 - 3540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-S. Liu, M. Jiang, M. Zhang, D. Tang, H. F. Clemo, R. S. D. Higgins, and G.-N. Tseng Electrical remodeling in a canine model of ischemic cardiomyopathy Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H560 - H571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-N. Tseng Linkage between 'disruption of inactivation' and 'reduction of K+ selectivity' among hERG mutants in the S5-P linker region J. Physiol., November 15, 2006; 577(1): 459 - 460. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Vandenberg, A. P. Hill, T. J. Campbell, and C. E. Clarke Reply from Jamie I. Vandenberg, Adam P. Hill, Terence J. Campbell, Catherine E. Clarke J. Physiol., November 15, 2006; 577(1): 461 - 462. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Clarke, A. P. Hill, J. Zhao, M. Kondo, R. N. Subbiah, T. J. Campbell, and J. I. Vandenberg Effect of S5P {alpha}-helix charge mutants on inactivation of hERG K+ channels J. Physiol., June 1, 2006; 573(2): 291 - 304. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
