Dynamic and clustering model of bacterial chemotaxis receptors: structural basis for signaling and high sensitivity.

Bacterial chemotaxis receptors can detect a small concentration gradient of attractants and repellents in the environment over a wide range of background concentration. The clustering of these receptors to form patches observed in vivo and in vitro has been suspected as a reason for the high sensitivity, and such wide dynamic range is thought to be due to the resetting of the receptor sensitivity threshold by methylation/demethylation of the receptors. However, the mechanisms by which such high sensitivity is achieved and how the methylation/demethylation resets the sensitivity are not well understood. A molecular modeling of an intact bacterial chemotaxis receptor based on the crystal structures of a cytoplasmic domain and a periplasmic domain suggests an interesting clustering of three dimeric receptors and a two-dimensional, close-packed lattice formation of the clusters, where each receptor dimer contacts two other receptor dimers at the cytoplasmic domain and two yet different receptor dimers at the periplasmic domain. This interconnection of the receptors to form a patch of receptor clusters suggests a structural basis for the high sensitivity of the bacterial chemotaxis receptors. Furthermore, we present crystallographic data suggesting that, in contrast to most molecular signaling by conformational changes and/or oligomerization of the signaling molecules, the changes in dynamic property of the receptors on ligand binding or methylation may be the language of the signaling by the chemotaxis receptors. Taken together, the changes of the dynamic property of one receptor propagating mechanically to many others in the receptor patch provides a plausible, simple mechanism for the high sensitivity and the dynamic range of the receptors.