Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel
Abstract
The selectivity filter of K{sup +} channels comprises four contiguous ion binding sites, S1 through S4. Structural and functional data indicate that the filter contains on average two K{sup +} ions at any given time and that these ions reside primarily in two configurations, namely to sites S1 and S3 or to sites S2 and S4. Maximum ion flux through the channel is expected to occur when the energy difference between these two binding configurations is zero. In this study, we have used protein semisynthesis to selectively perturb site 1 within the filter of the KcsA channel through use of an amide-to-ester substitution. The modification alters K{sup +} conduction properties. The structure of the selectivity filter is largely unperturbed by the modification, despite the loss of an ordered water molecule normally located just behind the filter. Introduction of the ester moiety was found to alter the distribution of K{sup +}, Rb{sup +}, and Cs{sup +} within the filter, with the most dramatic change found for Rb{sup +}. The redistribution of ions is associated with the appearance of a partially hydrated ion just external to the filter, at a position where no ion is observed in the wild-type channel. The appearancemore »
- Authors:
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Org.:
- Doe - Office Of Science
- OSTI Identifier:
- 914294
- Report Number(s):
- BNL-78862-2007-JA
Journal ID: ISSN 0002-7863; JACSAT; TRN: US200809%%152
- DOE Contract Number:
- DE-AC02-98CH10886
- Resource Type:
- Journal Article
- Resource Relation:
- Journal Name: J. Am. Chem. Soc.; Journal Volume: 128
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; DISTRIBUTION; ESTERS; FUNCTIONALS; MODIFICATIONS; POTASSIUM; PROTEINS; WATER; AMIDES; ION CHANNELING; national synchrotron light source
Citation Formats
Valiyaveetil,F., Sekedat, M., MacKinnon, R., and Muir, T. Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel. United States: N. p., 2006.
Web. doi:10.1021/ja0631955.
Valiyaveetil,F., Sekedat, M., MacKinnon, R., & Muir, T. Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel. United States. doi:10.1021/ja0631955.
Valiyaveetil,F., Sekedat, M., MacKinnon, R., and Muir, T. Sun .
"Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel". United States.
doi:10.1021/ja0631955.
@article{osti_914294,
title = {Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel},
author = {Valiyaveetil,F. and Sekedat, M. and MacKinnon, R. and Muir, T.},
abstractNote = {The selectivity filter of K{sup +} channels comprises four contiguous ion binding sites, S1 through S4. Structural and functional data indicate that the filter contains on average two K{sup +} ions at any given time and that these ions reside primarily in two configurations, namely to sites S1 and S3 or to sites S2 and S4. Maximum ion flux through the channel is expected to occur when the energy difference between these two binding configurations is zero. In this study, we have used protein semisynthesis to selectively perturb site 1 within the filter of the KcsA channel through use of an amide-to-ester substitution. The modification alters K{sup +} conduction properties. The structure of the selectivity filter is largely unperturbed by the modification, despite the loss of an ordered water molecule normally located just behind the filter. Introduction of the ester moiety was found to alter the distribution of K{sup +}, Rb{sup +}, and Cs{sup +} within the filter, with the most dramatic change found for Rb{sup +}. The redistribution of ions is associated with the appearance of a partially hydrated ion just external to the filter, at a position where no ion is observed in the wild-type channel. The appearance of this new ion-binding site creates a change in the distance between a pair of K{sup +} ions some fraction of the time, apparently leading to a reduction in the ion conduction rate. Importantly, this finding suggests that the selectivity filter of a potassium channel is optimized both in terms of absolute ion occupancy and in terms of the separation in distance between the conducting ions.},
doi = {10.1021/ja0631955},
journal = {J. Am. Chem. Soc.},
number = ,
volume = 128,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
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