Design of protein switches based on an ensemble model of allostery.

ABSTRACT: Switchable proteins that can be regulated through exogenous or endogenous inputs have a broad range of biotechnological and biomedical applications. Here we describe the design of switchable enzymes based on an ensemble allosteric model. First, we insert an enzyme domain into an effector-binding domain such that both domains remain functionally intact. Second, we induce the fusion to behave as a switch through the introduction of conditional conformational flexibility designed to increase the conformational entropy of the enzyme domain in a temperature- or pH-dependent fashion. We confirm the switching behaviour in vitro and in vivo. Structural and thermodynamic studies support the hypothesis that switching result from an increase in conformational entropy of the enzyme domain in the absen

SUBMITTER: Choi JH 

PROVIDER: S-EPMC4704092 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature