Water inside the selectivity filter of a K+ ion channel: structural heterogeneity, picosecond dynamics, and hydrogen-bonding.
Water inside the selectivity filter of a K+ ion channel: structural heterogeneity, picosecond dynamics, and hydrogen-bonding.
复制标题
K 离子通道选择性过滤器内的水：结构异质性、皮秒动力学和氢键。
DOI：
10.1101/2023.11.16.567415
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zanni,MartinT
中科院分区：
文献类型：
--
作者：
Ryan,MatthewJ;Gao,Lujia;Valiyaveetil,FrancisI;Kananenka,AlexeiA;Zanni,MartinT
生物离子通道内的水调节这些蛋白质的关键特性，如选择性、离子电导和门控。在这篇文章中，我们测量皮秒光谱扩散的酰胺I振动的同位素标记的KcsA钾通道使用二维红外（2D IR）光谱。通过结合等待时间（100-2000 fs）的二维红外测量的KcsA通道包括13 C18 O同位素标记的Val 76和Gly 77残基与分子动力学模拟，我们阐明了网站特定的动力学的水和K+离子内的选择性过滤的KcsA。我们观察到不均匀的二维线的形状与非常缓慢的光谱扩散。我们的模拟定量再现的实验表明，水是唯一的组件与任何明显的动态，而K+离子和蛋白质基本上是静态的皮秒时间尺度。通过分析模拟和实验的振动频率，我们发现，在选择性过滤器中的水可以定向形成氢键与相邻或不相邻的羰基与重取向的时标是三倍慢，相当于水分子在液体中，分别。水分子可以在离羰基足够远的空腔中存在，并且基本上表现为具有快速重定向时间的“自由”气相状水。值得注意的是，在皮秒时间尺度上没有观察到这些配置之间的相互转换。这些动态与液态水形成鲜明对比，液态水即使在高浓度离子存在下也保持高度动态。
Water inside biological ion channels regulates the key properties of these proteins, such as selectivity, ion conductance, and gating. In this article, we measure the picosecond spectral diffusion of amide I vibrations of an isotope-labeled KcsA potassium channel using two-dimensional infrared (2D IR) spectroscopy. By combining waiting time (100–2000 fs) 2D IR measurements of the KcsA channel including13C18O isotope-labeled Val76 and Gly77 residues with molecular dynamics simulations, we elucidated the site-specific dynamics of water and K+ions inside the selectivity filter of KcsA. We observe inhomogeneous 2D line shapes with extremely slow spectral diffusion. Our simulations quantitatively reproduce the experiments and show that water is the only component with any appreciable dynamics, whereas K+ions and the protein are essentially static on a picosecond timescale. By analyzing simulated and experimental vibrational frequencies, we find that water in the selectivity filter can be oriented to form hydrogen bonds with adjacent or nonadjacent carbonyl groups with the reorientation timescales being three times slower and comparable to that of water molecules in liquid, respectively. Water molecules can reside in the cavity sufficiently far from carbonyls and behave essentially like “free” gas-phase-like water with fast reorientation times. Remarkably, no interconversion between these configurations was observed on a picosecond timescale. These dynamics are in stark contrast with liquid water, which remains highly dynamic even in the presence of ions at high concentrations.
登录
查看更多内容
影响因子：
11.2
作者：
Toshiyuki Yoneda;M. Alsina;Kazuya Watatani;Francoise Bellot;Joseph Schlessinger;G. R. Mundy
通讯作者：
Toshiyuki Yoneda;M. Alsina;Kazuya Watatani;Francoise Bellot;Joseph Schlessinger;G. R. Mundy
影响因子：
6.4
作者：
OZAWA, S;UEDA, M;SHIMIZU, N
通讯作者：
SHIMIZU, N
瘤床效应通过缺氧细胞分数的增加诱导肿瘤放射治疗能力的降低。
DOI：
10.1016/0360-3016(89)90021-7
发表时间：
1989
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
Milas,L;Hunter,N;Peters,LJ
通讯作者：
Peters,LJ
N-甲基甲酰胺增强电离辐射对裸鼠异种移植的人结肠肿瘤的作用。
影响因子：
11.2
作者：
Dexter,DL;Lee,ES;Bliven,SF;Glicksman,AS;Leith,JT
通讯作者：
Leith,JT
苏拉明与肿瘤细胞放射敏感性
DOI：
--
发表时间：
1991
期刊：
影响因子：
--
作者：
J. Leith;S. Michelson
通讯作者：
S. Michelson