A distinct meta-active conformation in the 1.1-angstrom resolution structure of wild-type apoCheY

CheY is the best characterized member of the response regulator superfamily , and as such it has become the principal model for understanding the initi al molecular mechanisms of signaling in two-component systems. Normal signa ling by response regulators requires phosphorylation, in combination with a n activation mechanism whose conformational effects are not completely unde rstood. CheY activation involves three events, phosphorylation, a conformat ional. change in the beta (4)-alpha (4) loop, and a rotational restriction of the side chain of tyrosine 106. An outstanding question concerns the nat ure of an active conformation in the apoCheY population. The details of thi s 1.08-Angstrom resolution crystal structure of wild-type apoCheY shows the beta (4)-alpha (4) loop in two distinctly different conformations that ste rically correlate with the two rotameric positions of the tyrosine 106 side chain. One of these conformational states of CheY is the inactive form, an d we propose that the other is a meta-active form, responsible for the acti ve properties seen in apoCheY.