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1.
Coupling of agonist binding to channel gating in the GABA(A) receptor   总被引:7,自引:0,他引:7  
Kash TL  Jenkins A  Kelley JC  Trudell JR  Harrison NL 《Nature》2003,421(6920):272-275
Neurotransmitters such as acetylcholine and GABA (gamma-aminobutyric acid) mediate rapid synaptic transmission by activating receptors belonging to the gene superfamily of ligand-gated ion channels (LGICs). These channels are pentameric proteins that function as signal transducers, converting chemical messages into electrical signals. Neurotransmitters activate LGICs by interacting with a ligand-binding site, triggering a conformational change in the protein that results in the opening of an ion channel. This process, which is known as 'gating', occurs rapidly and reversibly, but the molecular rearrangements involved are not well understood. Here we show that optimal gating in the GABA(A) receptor, a member of the LGIC superfamily, is dependent on electrostatic interactions between the negatively charged Asp 57 and Asp 149 residues in extracellular loops 2 and 7, and the positively charged Lys 279 residue in the transmembrane 2-3 linker region of the alpha1-subunit. During gating, Asp 149 and Lys 279 seem to move closer to one another, providing a potential mechanism for the coupling of ligand binding to opening of the ion channel.  相似文献   

2.
Xu Y  Ramu Y  Lu Z 《Nature》2008,451(7180):826-829
A fundamental question about the gating mechanism of voltage-activated K+ (Kv) channels is how five positively charged voltage-sensing residues in the fourth transmembrane segment are energetically stabilized, because they operate in a low-dielectric cell membrane. The simplest solution would be to pair them with negative charges. However, too few negatively charged channel residues are positioned for such a role. Recent studies suggest that some of the channel's positively charged residues are exposed to cell membrane phospholipids and interact with their head groups. A key question nevertheless remains: is the phospho-head of membrane lipids necessary for the proper function of the voltage sensor itself? Here we show that a given type of Kv channel may interact with several species of phospholipid and that enzymatic removal of their phospho-head creates an insuperable energy barrier for the positively charged voltage sensor to move through the initial gating step(s), thus immobilizing it, and also raises the energy barrier for the downstream step(s).  相似文献   

3.
Ramsey IS  Moran MM  Chong JA  Clapham DE 《Nature》2006,440(7088):1213-1216
Voltage changes across the cell membrane control the gating of many cation-selective ion channels. Conserved from bacteria to humans, the voltage-gated-ligand superfamily of ion channels are encoded as polypeptide chains of six transmembrane-spanning segments (S1-S6). S1-S4 functions as a self-contained voltage-sensing domain (VSD), in essence a positively charged lever that moves in response to voltage changes. The VSD 'ligand' transmits force via a linker to the S5-S6 pore domain 'receptor', thereby opening or closing the channel. The ascidian VSD protein Ci-VSP gates a phosphatase activity rather than a channel pore, indicating that VSDs function independently of ion channels. Here we describe a mammalian VSD protein (H(V)1) that lacks a discernible pore domain but is sufficient for expression of a voltage-sensitive proton-selective ion channel activity. H(v)1 currents are activated at depolarizing voltages, sensitive to the transmembrane pH gradient, H+-selective, and Zn2+-sensitive. Mutagenesis of H(v)1 identified three arginine residues in S4 that regulate channel gating and two histidine residues that are required for extracellular inhibition of H(v)1 by Zn2+. H(v)1 is expressed in immune tissues and manifests the characteristic properties of native proton conductances (G(vH+)). In phagocytic leukocytes, G(vH+) are required to support the oxidative burst that underlies microbial killing by the innate immune system. The data presented here identify H(v)1 as a long-sought voltage-gated H+ channel and establish H(v)1 as the founding member of a family of mammalian VSD proteins.  相似文献   

4.
Schmidt D  Jiang QX  MacKinnon R 《Nature》2006,444(7120):775-779
Cells communicate with their external environment through physical and chemical processes that take place in the cell-surrounding membrane. The membrane serves as a barrier as well as a special environment in which membrane proteins are able to carry out important processes. Certain membrane proteins have the ability to detect the membrane voltage and regulate ion conduction or enzyme activity. Such voltage-dependent processes rely on the action of protein domains known as voltage sensors, which are embedded inside the cell membrane and contain an excess of positively charged amino acids, which react to an electric field. How does the membrane create an environment suitable for voltage sensors? Here we show under a variety of conditions that the function of a voltage-dependent K+ channel is dependent on the negatively charged phosphodiester of phospholipid molecules. A non-voltage-dependent K+ channel does not exhibit the same dependence. The data lead us to propose that the phospholipid membrane, by providing stabilizing interactions between positively charged voltage-sensor arginine residues and negatively charged lipid phosphodiester groups, provides an appropriate environment for the energetic stability and operation of the voltage-sensing machinery. We suggest that the usage of arginine residues in voltage sensors is an adaptation to the phospholipid composition of cell membranes.  相似文献   

5.
随着现代工业的发展,X射线无损探伤技术应用越来越广,而其是否真正做到无损有待深刻研究。实验先通过X射线仪对聚乙烯材料进行不同强度和不同时间的照射,并对照射后的试样进行介电常数测试和xrd衍射表征来分析射线对试样的伤害。研究其介电常数的变化对无损探伤技术有着重大指导意义。实验发现X射线照射时间和强度对绝缘材料聚乙烯的介电常数有不同程度影响,但按照合理的照射时间和强度,可将材料性能控制在工业标准之内。  相似文献   

6.
Boudker O  Ryan RM  Yernool D  Shimamoto K  Gouaux E 《Nature》2007,445(7126):387-393
Secondary transporters are integral membrane proteins that catalyse the movement of substrate molecules across the lipid bilayer by coupling substrate transport to one or more ion gradients, thereby providing a mechanism for the concentrative uptake of substrates. Here we describe crystallographic and thermodynamic studies of Glt(Ph), a sodium (Na+)-coupled aspartate transporter, defining sites for aspartate, two sodium ions and d,l-threo-beta-benzyloxyaspartate, an inhibitor. We further show that helical hairpin 2 is the extracellular gate that controls access of substrate and ions to the internal binding sites. At least two sodium ions bind in close proximity to the substrate and these sodium-binding sites, together with the sodium-binding sites in another sodium-coupled transporter, LeuT, define an unwound alpha-helix as the central element of the ion-binding motif, a motif well suited to the binding of sodium and to participation in conformational changes that accompany ion binding and unbinding during the transport cycle.  相似文献   

7.
本文将配置法应用于研究带电粒子悬浮液的有效交流复电导率.研究表明,在相当宽的粒子浓度范围内,配置方法十分有效.配置方法不受悬浮液中两相介质的介电系数相等这一条件的限制,从而为进一步研究带电颗粒悬浮液的宏观物理性质提供了一条有效的途径.  相似文献   

8.
本文应用正电子湮没寿命谱方法研究掺杂SrTiO_3陶瓷的介电性.通过对不同掺La量SrTiO_3的介电常数、损耗因子、正电子在样品中的湮没寿命的测量,发现介电常数、损耗因子随掺La量的变化与正电子寿命参量的变化存在着某种关系;文中用Sr空位及La离子与Sr空位缔合体模型解释了这些变化与关系.  相似文献   

9.
利用Maxwell-Wagner模型,同时采用John Lam在磁流变体中研究磁导率的迭代方法,研究了电流变体中3种结构的立方格子导电球的有效介电常数与频率的依赖关系.结果发现,有效介电常数依赖于外加电场的频率,在高频条件下ω≥0.1-1 kHz,有效介电常数依赖于导电球与流体的介电常数比,而在低频或直流条件下,是电导率起主要作用.所得结果与相关实验结果基本吻合.  相似文献   

10.
利用格子Boltzmann方法分别模拟了在同等初始条件下释放的单个带电和不带电弹性哑铃在牛顿流体中的运动.模拟所得的数值结果表明,对于单个不带电的弹性哑铃,当其被置于质心偏离管道中心线的初始位移处水平地释放后,弹性哑铃逐渐向管道的中心线漂移,当其质心漂移到达管道中心线后,弹性哑铃呈现稳定的垂直下落状态,在沉降运动中,弹性哑铃的方向保持水平方向不变.对于同等初始条件下释放的单个带电弹性哑铃,当流体的介电常数小于管道壁的介电常数时,由于静电极化的作用,弹性哑铃在其沉降过程中将受到管道壁的吸引力,该力使得弹性哑铃的运动发生显著的改变,以至于它处于最终垂直下落状态时,其质心尚未到达管道的中心线.  相似文献   

11.
陈钢  苏同福  赵士举 《河南科学》2014,(11):2233-2236
为了探讨萃取剂与银杏叶总黄酮的极性和结构关系,研究萃取剂极性对于银杏叶总黄酮提取效率的影响.实验采用微波萃取的方法,研究体积分数为80%的乙醇、80%丙酮、80%正丁醇3种不同极性的溶剂对银杏叶黄酮提取率的影响.实验结果表明,80%正丁醇对银杏叶总黄酮的提取效率最高,80%乙醇次之,80%丙酮最低,与介电常数测定结果中80%正丁醇的介电常数和银杏叶黄酮的介电常数最接近一致.  相似文献   

12.
Ferroelectric thin films and superlattices are currently the subject of intensive research because of the interest they raise for technological applications and also because their properties are of fundamental scientific importance. Ferroelectric superlattices allow the tuning of the ferroelectric properties while maintaining perfect crystal structure and a coherent strain, even throughout relatively thick samples. This tuning is achieved in practice by adjusting both the strain, to enhance the polarization, and the composition, to interpolate between the properties of the combined compounds. Here we show that superlattices with very short periods possess a new form of interface coupling, based on rotational distortions, which gives rise to 'improper' ferroelectricity. These observations suggest an approach, based on interface engineering, to produce artificial materials with unique properties. By considering ferroelectric/paraelectric PbTiO3/SrTiO3 multilayers, we first show from first principles that the ground-state of the system is not purely ferroelectric but also primarily involves antiferrodistortive rotations of the oxygen atoms in a way compatible with improper ferroelectricity. We then demonstrate experimentally that, in contrast to pure PbTiO3 and SrTiO3 compounds, the multilayer system indeed behaves like a prototypical improper ferroelectric and exhibits a very large dielectric constant of epsilon(r) approximately 600, which is also fairly temperature-independent. This behaviour, of practical interest for technological applications, is distinct from that of normal ferroelectrics, for which the dielectric constant is typically large but strongly evolves around the phase transition temperature and also differs from that of previously known improper ferroelectrics that exhibit a temperature-independent but small dielectric constant only.  相似文献   

13.
2.45 GHz不同条件对冰复介电常数测量影响的实验研究   总被引:1,自引:0,他引:1  
用谐振腔微扰法在微波频率2.45 GHz下对冰的复介电常数的进行了测量,着重研究了不同浓度的杂质金属离子(Na+, K+ ,Ca2+)和不同平均输出功率微波加热二次去离子水至沸腾后结成冰的复介电常数的影响.测量结果表明,冰的复介电常数的实部与杂质离子浓度成线性关系,而虚部则成非线性关系,并且不同平均输出功率的微波加热后的冰的复介电常数实部不同.  相似文献   

14.
Biertümpfel C  Yang W  Suck D 《Nature》2007,449(7162):616-620
Holliday proposed a four-way DNA junction as an intermediate in homologous recombination, and such Holliday junctions have since been identified as a central component in DNA recombination and repair. Phage T4 endonuclease VII (endo VII) was the first enzyme shown to resolve Holliday junctions into duplex DNAs by introducing symmetrical nicks in equivalent strands. Several Holliday junction resolvases have since been characterized, but an atomic structure of a resolvase complex with a Holliday junction remained elusive. Here we report the crystal structure of an inactive T4 endo VII(N62D) complexed with an immobile four-way junction with alternating arm lengths of 10 and 14 base pairs. The junction is a hybrid of the conventional square-planar and stacked-X conformation. Endo VII protrudes into the junction point from the minor groove side, opening it to a 14 A x 32 A parallelogram. This interaction interrupts the coaxial stacking, yet every base pair surrounding the junction remains intact. Additional interactions involve the positively charged protein and DNA phosphate backbones. Each scissile phosphate that is two base pairs from the crossover interacts with a Mg2+ ion in the active site. The similar overall shape and surface charge potential of the Holliday junction resolvases endo VII, RuvC, Ydc2, Hjc and RecU, despite having different folds, active site composition and DNA sequence preference, suggest a conserved binding mode for Holliday junctions.  相似文献   

15.
研究了梯度壳层球形颗粒复合体系的有效介电响应,推导了具有任意多壳层的球形颗粒的等效介电常数的一般递推公式;用微分有效偶极近似的方法推导出任意介电梯度形式球形颗粒的等效介电常数的一般微分方程,并以壳层的介电常数为半径的幂函数形式为例,得到了梯度壳层球形颗粒的等效介电常数.从而在极稀释条件下,根据Maxwell-Garnett近似(MGA),得到了梯度壳层球形颗粒复合体系的有效介电常数.  相似文献   

16.
本文分析了便携式电子设备中锂离子电池运用恒定电压、恒定电流的充电技术的原理,充电期间对锂离子电池的保护措施及其应用。  相似文献   

17.
本文导出一般形式的Rayleigh方程和混杂介质的有效介电常数公式,计算了介电粒子构成的六角密堆积结构的有效介电常经,从理论上讲.笔者的计算可准确到任意高阶矩,因而结果是精确的。  相似文献   

18.
应用苄基三乙基氯化胺作相转移催化剂,在氢氧化钠水溶液和醇中反应,分离出一种反应中间体离子对Q~+-OR(Q~+=(?)—CH_2(?)(C_2H_5)_3,R=CH_3,C_2H_5)。用实验方法证实了硝基氟苯和醇,氢氧化钠通过季铵盐相转移催化剂合成硝基苯烷醚,该反应是按照C. M. Starks提出的相转移催化机理进行的。  相似文献   

19.
用X和射线衍射、透射电镜、扫描电镜、介电性能与电导平衡等方法研究了B位Ca离子对BaTiO_3;陶瓷铁电相变的影响.X射线衍射数据表明,随着B位Ca离子含量的增加(直至5%)c/a比下降至接近1.从介电系数的温度关系可见:含5%B位与6%A位Ca离子的组份其居里峰展宽且下降至室温.发现了当含A位Ca离子(约5%)时,B位Ca离子含量的变化对降低居里点有较显著的作用.据此结果,本文发展了一套热力学模型以解释Ca掺杂BaTiO_3中B位Ca离子对居里峰移动与展宽的作用.  相似文献   

20.
冻土介电常数的实验研究   总被引:6,自引:0,他引:6  
探讨了冻土介电常数的测量方法,通过实验初步研究了冻土介电常数随频率、温度和含水量的变化规律.  相似文献   

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