S. Djordjevic et al., STRUCTURAL BASIS FOR METHYLESTERASE CHEB REGULATION BY A PHOSPHORYLATION-ACTIVATED DOMAIN, Proceedings of the National Academy of Sciences of the United Statesof America, 95(4), 1998, pp. 1381-1386
We report the x-ray crystal structure of the methylesterase CheB, a ph
osphorylation-activated response regulator involved in reversible modi
fication of bacterial chemotaxis receptors, Methylesterase CheB and me
thyltransferase CheR modulate signaling output of the chemotaxis recep
tors by controlling the level of receptor methylation, The structure o
f CheB, which consists of an N-terminal regulatory domain and a C-term
inal catalytic domain joined by a linker, was solved by molecular repl
acement methods using independent search models for the two domains, I
n unphosphorylated CheB, the N-terminal domain packs against the activ
e site of the C-terminal domain and thus inhibits methylesterase activ
ity by directly restricting access to the active site, We propose that
phosphorylation of CheB induces a conformational change in the regula
tory domain that disrupts tile domain interface, resulting in a reposi
tioning of the domains and allowing access to the active site, Structu
ral similarity between the two companion receptor modification enzymes
, CheB and CheR, suggests an evolutionary and/or functional relationsh
ip, Specifically, the phosphorylated N-terminal domain of CheB may fac
ilitate interaction with the receptors, similar to the postulated role
of the N-terminal domain of CheR. Examination of surfaces in the N-te
rminal regulatory domain of CheB suggests that despite a common fold t
hroughout the response regulator family, surfaces used for protein-pro
tein interactions differ significantly, Comparison between CheB and ot
her response regulators indicates that analogous surfaces are used for
different functions and conversely, similar functions are mediated by
different molecular surfaces.