期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 2, 页码 598-602出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1013636108
关键词
nonselective cation channel; potassium channel
资金
- US Department of Energy, Office of Energy Research
- The Howard Hughes Medical Institute
- National Institute of Health (NIH) [GM079179, 5 F31 GM07703, T32 GM008297]
- The David and Lucile Packard Foundation
- Welch Foundation [I-1578]
Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K+ channel selectivity filters. Combined with single channel electrophysiology, we show that only the channel with four ion binding sites is K+ selective, whereas those with two or three are nonselective and permeate Na+ and K+ equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K+ channels is essential for highly selective and efficient permeation of K+ ions.
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