Instantaneous ion configurations in the K+ ion channel selectivity filter revealed by 2D IR spectroscopy

被引:167
作者
Kratochvil, Huong T. [1 ]
Carr, Joshua K. [1 ]
Matulef, Kimberly [2 ]
Annen, Alvin W. [2 ]
Li, Hui [3 ]
Maj, Michal [1 ]
Ostmeyer, Jared [3 ]
Serrano, Arnaldo L. [1 ]
Raghuraman, H. [3 ,4 ]
Moran, Sean D. [1 ,5 ]
Skinner, J. L. [1 ]
Perozo, Eduardo [3 ]
Roux, Benoit [3 ]
Valiyaveetil, Francis I. [2 ]
Zanni, Martin T. [1 ]
机构
[1] Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA
[2] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Program Chem Biol, Portland, OR 97239 USA
[3] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA
[4] Saha Inst Nucl Phys, Crystallog & Mol Biol Div, Kolkata 700064, W Bengal, India
[5] Southern Illinois Univ, Dept Chem & Biochem, Carbondale, IL 62901 USA
基金
美国国家卫生研究院;
关键词
POTASSIUM-CHANNEL; CONDUCTION; KCSA; MECHANISM; PROTEINS; BINDING; PERMEATION; ENERGETICS;
D O I
10.1126/science.aag1447
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Potassium channels are responsible for the selective permeation of K+ ions across cell membranes. K+ ions permeate in single file through the selectivity filter, a narrow pore lined by backbone carbonyls that compose four K+ binding sites. Here, we report on the two-dimensional infrared (2D IR) spectra of a semisynthetic KcsA channel with site-specific heavy ((CO)-C-13-O-18) isotope labels in the selectivity filter. The ultrafast time resolution of 2D IR spectroscopy provides an instantaneous snapshot of the multi-ion configurations and structural distributions that occur spontaneously in the filter. Two elongated features are resolved, revealing the statistical weighting of two structural conformations. The spectra are reproduced by molecular dynamics simulations of structures with water separating two K+ ions in the binding sites, ruling out configurations with ions occupying adjacent sites.
引用
收藏
页码:1040 / 1044
页数:5
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