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CheB is an enzyme that reverses receptor methylation in chemotaxis; its regulation contributes to negative feedback.

CheR is an enzyme that catalyzes receptor methylation in chemotaxis, contributing to signaling adaptation.

Negative feedback closes a causal loop whose net effect opposes an initiating change. In signal transduction, activation followed by a downstream inhibition of the earlier activating stage is one example of negative feedback. Loop sign alone does not establish asymptotic stability or complete signaling adaptation; see the worked signaling feedback example.

A useful biological example is chemotaxis feedback regulation: an Escherichia coli biological cell adjusts its response to a sustained attractant instead of remaining at its immediate response. Increased CheA activity promotes CheB phosphorylation; CheB reverses receptor methylation, opposing their activation. After attractant addition, reduced activity instead favors receptor methylation by CheR, restoring activity. This is a return from receptor activity to the machinery regulating that activity. The response need not return exactly at every dose. ^[ref]

A motivating measurement is the chemotaxis FRET assay. CheY and CheZ carrying yellow and cyan fluorescent tags were observed in immobilized Escherichia coli biological cells on a coverslip in a flow chamber. Adding and removing attractant changed the yellow-to-cyan emission ratio, reporting the association of phosphorylated CheY with CheZ. This measures a molecular readout upstream of motor behavior. Comparisons with biological cells lacking CheR, CheB, or both tested the dependence on receptor modification; these perturbations also change starting activity and sensitivity, so they are not pure changes of one feedback gain. ^[ref]

The later chemotaxis feedback regulation experiment used only the Tar receptor and nonmetabolizable methylaspartate, supplied and removed by flow. Long recordings separated slow recovery from incomplete signaling adaptation; correction for bleaching addressed drift in the optical readout. Activity recovered incompletely after sufficiently large additions, with detectable imprecision already at $10\mu \mathrm{M}$ in that preparation. Restricting the receptor type and preventing consumption of the stimulus help interpret the perturbation, but limit transfer to other receptors and conditions. The readout infers CheA activity through CheY-CheZ association, rather than directly measuring every molecular step. ^[ref]

Negative feedback can also overshoot or sustain oscillations if its return arrives too late. The worked signaling feedback example gives the contrasting instantaneous case; the delayed negative feedback model below isolates the effect of timing. Loop sign describes causation, while asymptotic stability describes what happens to displacements over time.