Structural and thermodynamic properties of selective ion binding in a K+ channel.
Structural and thermodynamic properties of selective ion binding in a K+ channel.
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DOI：
10.1371/journal.pbio.0050121
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发表时间：
2007-05
期刊：
影响因子：
9.8
通讯作者：
MacKinnon R
中科院分区：
文献类型：
--
作者：
Lockless SW;Zhou M;MacKinnon R
使用等温滴定量热法进行离子结合的变铅青链霉菌K+通道的热力学测量，而离子结合和离子自由构象的通道的原子结构，其特征在于通过X-射线晶体学。在这里，我们使用这些测定来表明选择性的离子半径依赖性源于通道对离子大小的识别（即，体积）而不是电荷密度。离子大小识别是通道采用非常特定的导电结构的能力的函数，该结构与较大的离子（K+、Rb+、Cs+和Ba 2+）结合，而不与较小的离子（Na+、Mg 2+和Ca 2+）结合。导电结构的形成涉及与结合离子直接接触的选择性过滤器原子以及围绕选择性过滤器的距离离子高达15 μ m的蛋白质原子。我们的结论是，在K+通道的离子选择性是由蛋白质结构的大小匹配的离子结合位点的属性。细胞膜中钾离子（K+）通道的精确选择性允许它们通过K+离子，同时限制密切相关的钠（Na+）离子，从而保持跨细胞膜的电位。在这项研究中，我们解决的基本问题：如何K+通道区分K+和Na+离子？过去的研究依赖于离子电流的非平衡测量。我们测量了热交换与离子结合的通道在平衡条件下，并确定离子结合和离子自由形式的通道的晶体结构。通过研究一系列碱金属和碱土金属阳离子，我们记录了系统地改变离子电荷和半径的效果，我们发现K+通道识别离子的大小，而不是其电场强度。通过分析结构，我们表明，通道的能力，以识别离子的大小是一个功能的蛋白质原子，都接近和远离离子结合位点。这项研究打开了一个新的窗口，离子选择性通道，也有助于我们扩大知识的新兴作用的长程相互作用在配体识别。KcSA K+通道的离子选择性通过结合离子结合的热力学测量和离子结合和无离子构象的结构分析来评估。
Thermodynamic measurements of ion binding to the Streptomyces lividans K+ channel were carried out using isothermal titration calorimetry, whereas atomic structures of ion-bound and ion-free conformations of the channel were characterized by x-ray crystallography. Here we use these assays to show that the ion radius dependence of selectivity stems from the channel's recognition of ion size (i.e., volume) rather than charge density. Ion size recognition is a function of the channel's ability to adopt a very specific conductive structure with larger ions (K+, Rb+, Cs+, and Ba2+) bound and not with smaller ions (Na+, Mg2+, and Ca2+). The formation of the conductive structure involves selectivity filter atoms that are in direct contact with bound ions as well as protein atoms surrounding the selectivity filter up to a distance of 15 Å from the ions. We conclude that ion selectivity in a K+ channel is a property of size-matched ion binding sites created by the protein structure. The exquisite selectivity of potassium ion (K+) channels in cellular membranes allows them to pass K+ ions while restricting the closely related sodium (Na+) ions, and thereby maintain the electrical potential across cellular membranes. In this study, we address the fundamental question: how does the K+ channel discriminate between K+ and Na+ ions? Past studies have relied on nonequilibrium measurements of ionic current flow. We measured heat exchange associated with ion binding to the channel under equilibrium conditions and determined crystal structures of ion-bound and ion-free forms of the channel. By studying a series of alkali metal and alkaline earth cations, we documented the effect of varying systematically the ionic charge and radius, and we discovered that the K+ channel recognizes an ion's size rather than its electric field strength. By analyzing the structures, we show that the channel's ability to recognize an ion's size is a function of protein atoms that are both near to and far away from the ion binding sites. This study opens a new window into ion selectivity in channels and also contributes to our expanding knowledge of the emerging role of long-range interactions in ligand recognition. Ion selectivity of the KcSA K+ channel is assessed through a combination of thermodynamic measurements of ion binding and structural analysis of ion-bound and ion-free conformations.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1038/nsb881
发表时间：
2003-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Süel, GM;Lockless, SW;Ranganathan, R
通讯作者：
Ranganathan, R
影响因子：
1.8
作者：
KAUFFMANN, E;LEHN, JM;SAUVAGE, JP
通讯作者：
SAUVAGE, JP
影响因子：
64.8
作者：
Noskov, SY;Bernèche, S;Roux, B
通讯作者：
Roux, B
离散的BA2+块作为高导通Ca2+活化的K+通道中离子占用和孔结构的探针。
影响因子：
3.8
作者：
Neyton, J;Miller, C
通讯作者：
Miller, C