Transformation

Abstract

The textbook view that a primary sequence determines the unique fold of a given protein has been challenged by identification of proteins with variant structures, such as prions. Our recent studies revealed that the transcription factor RfaH simultaneously changes its topology and function. RfaH is a two-domain protein whose N-terminal domain binds to transcribing RNA polymerase, stimulating its processivity. The α-helical C-terminal domain masks the RNA polymerase-binding site of the N-terminal domain, preventing unwarranted recruitment to genes lacking a specific DNA sequence. Upon binding to its DNA target, RfaH domains dissociate, and the C-terminal domain refolds into a β-barrel. This dramatic transformation allows binding to the ribosomal protein S10 and subsequent recruitment of a ribosome, coupling transcription and translation. We define RfaH as first example of “transformer proteins”, in which two alternative structural states have distinct cellular functions and hypothesize that transformer proteins may be widespread in nature.

Keywords: :

• RfaH
• NusG
• transcription factor
• transformer protein
• moonlighting protein
• metamorphic protein
• ops DNA
• multifunctionality
• protein folding
• refolding

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (Ro617/18–1) and the National Institutes of Health (GM67153).