Receptor dissociation constants and the information entropy of membranes coding ligand concentration.
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.
Division of Insect Biology, Department of ESPM, University of California, Berkeley, CA 94720-3112, USA. getz@nature.berkeley.edu
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000378:metabolism; D019277:Entropy; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D008954:Models, Biological; D009036:Moths; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015290:Second Messenger Systems; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D008024:Ligands; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2