TI - The concentration of CheYp in non-stimulated cells . AB - While the differential-affinity-and-catalytic-activity model can describe the dose-response curves as reported by Vaknin and Berg [2] , a number of issues remain . The first is that in the full differential-affinity-and-catalytic-activity model , which takes into account CheZ cooperativity , the total concentration of [Yp] in non-stimulated CheZ mutant cells is on the border of the working range of the motor , while experiments on mutant cells lacking CheAs , which plays a role in localizing CheZ to the receptor cluster [12] , suggest that CheZ mutant cells can chemotax . This raises an interesting question , which to our knowledge has not been studied yet : How strongly does the efficiency of chemotaxis depend upon the concentration of CheYp in the adapted state? In particular , how well must that be inside the working range of the motor? It is conceivable that cells with [Yp] at the high end of the motor's working range can chemotax , albeit less efficiently . Another possibility is that CheZ mutant cells can chemotax , because [Yp] forms spatial gradients inside CheZ mutant cells [2] : while [Yp] at some motors will be outside the motor's working range , [Yp] at other motors might be inside the working range of the motor . But perhaps the most likely explanation is that PHOSphorylation of CheB by CheAp provides a negative feedback loop on the activity of the receptor cluster that tends to keep the concentration of CheYp within a certain range . The concentration of CheYp in the adapted state is determined by the activity of the receptor cluster in the adapted state , which is controlled by the activity of the methylation and demethylation enzymes CheR and CheB , respectively . CheAp cannot only PHOSphorylate CheY , but also CheB . Moreover , phosphorylaTED CheB has a higher demethylation activity than unPHOSphorylated CheB . Since CheY and CheB compete with one another for phosphorylaTION by CheAp , the concentration of PHOSphorylated CheB increases as [Yp] increases and [Y] decreases [35] . However , since PHOSphorylated CheB has a higher demethylation activity , this tends to lower the activity of the receptor cluster , which in turn tends to lower [Yp] . In our model , the activity of the receptor cluster is assumed to be the same for wild-type and CheZ mutant cells and it was chosen such that the concentration of CheYp in adapted wild-type cells is within the working range of the motor . Yet , it is conceivable that because of the negative feedback loop , the activity of the receptor cluster in the adapted state is lower in CheZ mutant cells than in CheZ wild-type cells . This would lower the concentration of CheYp in the CheZ mutant cells and could bring it within the motor's range .