Serial rebinding of ligands to clustered receptors as exemplified by bacterial chemotaxis

Serial ligation is the repeated reversible binding of a ligand to one receptor after another. It is a widespread phenomenon throughout biochemical systems, occurring anytime receptors are clustered together and ligand binding is reversible. Computer simulations are used in this work to investigate a representative example, which is the serial ligation of an extracellular aspartate molecule to the membrane-bound chemotaxis receptors of an Escherichia coli bacterium. It is found that the initial binding site of a ligand to a cluster of receptors is more likely to be near the edge of the cluster than near the middle, although there is no overall bias when all rebindings are considered. Serial ligation does not lead directly to signal amplification or attenuation but instead causes binding events to be correlated in both space and time: a ligand is likely to bind many times in rapid succession in a small region of the receptor cluster, but there can also be long intervals between bindings. This leads to an increased level of noise in the received signal but may allow a single ligand to be sensed above a uniform level of background noise. The focus of this paper is on the interpretation of simulation results so they can be generalized to a wide variety of other systems and to allow the identification of systems in which serial ligation is likely to be important. In the process, several characteristic times are identified, as are scaling laws for the spatial and temporal dynamics.