A protein functional leap: how a single mutation reverses the function of the transcription regulator TetR.

ABSTRACT: Today's proteome is the result of innumerous gene duplication, mutagenesis, drift and selection processes. Whereas random mutagenesis introduces predominantly only gradual changes in protein function, a case can be made that an abrupt switch in function caused by single amino acid substitutions will not only considerably further evolution but might constitute a prerequisite for the appearance of novel functionalities for which no promiscuous protein intermediates can be envisaged. Recently, tetracycline repressor (TetR) variants were identified in which binding of tetracycline triggers the repressor to associate with and not to dissociate from the operator DNA as in wild-type TetR. We investigated the origin of this activity reversal by limited proteolysis, CD spectroscopy and X-ray crysta

SUBMITTER: Resch M 

PROVIDER: S-EPMC2490752 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature