Getz W M, Lánsky P
Division of Insect Biology, Department of ESPM, University of California, Berkeley, CA 94720-3112, USA.
Chem Senses. 2001 Feb;26(2):95-104. doi: 10.1093/chemse/26.2.95.
The binding of ligands to receptor proteins embedded in cell membranes drives cellular responses that involve either second messenger cascades or directly gated ion channels. It is known that a single class of receptor proteins expresses approximately 98% of its graded response to ligand concentrations over four orders of magnitude, where the response is measured by the equilibrium proportion of bound ligand-receptor complexes. This four-decadic concentration range is centered on a logarithmic scale around logK, where K is the dissociation constant defined by the ratio of ligand-receptor unbinding (k-) to binding (k+) rates. Remarkably, this four-decadic concentration range is intrinsic to all homogeneous ligand-receptor (or, equivalently, enzyme-substrate) systems. Thus, adapting the sensitivity of cell membranes to narrower or wider ranges of ligand concentrations, respectively, requires multivalent receptors or heterogeneous populations of receptors. Here we use a normalized Shannon-Weaver measure of information entropy to represent the efficiency of coding over given concentrations for membranes containing a population of univalent receptors with a specified distribution of dissociation constants, or a homogeneous population of strongly cooperative multivalent receptors. Assuming a specified level of resolution in the response of cellular or neural systems downstream from the membrane that 'read' the ligand concentration 'code', we calculate the range of concentrations over which the coding efficiency of the membrane itself is maximized. Our results can be used to hypothesize the number of receptor types associated with the membranes of particular cells. For example, from data in the literature, we conclude that the response of most general olfactory sensory neurons can be explained in terms of a homogeneous population of receptor proteins, while the response of pheromone sensory neurons is satisfactorily explained by the presence of two types of membrane receptor protein with pheromone-binding dissociation constants that have values at least one to two orders of magnitude apart.
配体与嵌入细胞膜中的受体蛋白结合会驱动细胞反应，这些反应涉及第二信使级联反应或直接门控离子通道。已知一类受体蛋白在四个数量级的配体浓度范围内，对其分级反应的表达约为98%，其中反应通过结合的配体 - 受体复合物的平衡比例来衡量。这个四个数量级的浓度范围在以logK为中心的对数尺度上，其中K是由配体 - 受体解离（k-）与结合（k+）速率之比定义的解离常数。值得注意的是，这个四个数量级的浓度范围是所有均匀配体 - 受体（或等效地，酶 - 底物）系统所固有的。因此，要使细胞膜对配体浓度范围分别变窄或变宽的敏感性进行调整，就需要多价受体或受体的异质群体。在这里，我们使用归一化的香农 - 韦弗信息熵度量来表示对于含有具有特定解离常数分布的单价受体群体或强协同多价受体均匀群体的膜，在给定浓度上的编码效率。假设在“读取”配体浓度“代码”的膜下游的细胞或神经系统反应中有指定的分辨率水平，我们计算膜本身编码效率最大化的浓度范围。我们的结果可用于推测与特定细胞膜相关的受体类型数量。例如，根据文献中的数据，我们得出结论，大多数普通嗅觉感觉神经元的反应可以用受体蛋白的均匀群体来解释，而信息素感觉神经元的反应可以通过存在两种类型的膜受体蛋白来令人满意地解释，这两种蛋白的信息素结合解离常数的值至少相差一到两个数量级。
