Recent progress with FKBP-derived destabilizing domains

The FKBP-derived destabilizing domains are increasingly being used to confer small molecule-dependent stability to many different proteins. The L106P domain confers instability to yellow fluorescent protein when it is fused to the N-terminus, the C-terminus, or spliced into the middle of yellow fluorescent protein, however multiple copies of L106P do not confer greater instability. These engineered destabilizing domains are not dominant to endogenous degrons that regulate protein stability.

We recently engineered mutants of the FKBP12 protein that are rapidly degraded when expressed in cells. Recent results expand the utility of this general technology to provide small molecule control over protein stability.Figure optionsDownload as PowerPoint slide