Fig 13.

Negative (A) and positive (B) control of AAA⁺ domain activity. In the more common mechanism of negative control, ligand binding (or phosphorylation) relieves the repression of the regulatory (R) domain on the central (C) domain, which is intrinsically competent to hydrolyze ATP. The AAA⁺ domain is then able to carry out ATP hydrolysis. Accordingly, when the R domain is removed, the bEBP is active irrespective of the presence or absence of a signaling molecule (shown as a purple triangle) or an available kinase. In positive control, ligand binding or phosphorylation has a genuine stimulatory function. The phosphorylated or ligand-bound form of the R domain activates the C domain, which is not intrinsically competent to hydrolyze ATP. The AAA⁺ domain is then able to carry out ATP hydrolysis. Accordingly, when the R domain is removed, the bEBP is inactive irrespective of the presence or absence of a signaling molecule or an available kinase.