First experimental evidence of dynamic allostery in protein regulation thanks to NMR
Regulation of gene transcription is a mechanism that allows cells to adapt to rapidly changing environmental conditions. In prokaryotes, genes are typically clustered in operons with each operon being regulated as an entity. The toxin-antitoxin (TA) system, which plays a role in stress, is one instance of this process.
Abel Garcia-Pino and his colleagues study the Phd-Doc toxin-antitoxin operon of P1 bacteriophages (small viruses) under the leadership of Remy Loris. Until now, no one has been able to explain the regulatory mechanism of this system at the molecular level. Hence, these VIB researchers are the first to demonstrate that, when Doc binds to the intrinsically unfolded C-terminus of Phd, it structures the DNA-binding domain of Phd. This type of communication process between two protein domains is called allostery. Already in the sixties allostery was generally assumed to be an important regulation mechanism in enzymes and Monod even called it the second secret of life (the first one being the genetic code). Several years ago, allostery between intrinsically unfolded protein domains became accepted, based on theoretical models, but now it has been experimentally demonstrated for the first time. The regulation mechanism presented here is new and probably also applies to other genes.
The NMR technology is the only technology that can detect and quantify folding and conformational changes in proteins while simultaneously providing detailed structural information. Besides its applications in fundamental biology, NMR is also a promising technology for the identification of therapeutic drugs.
|Contact: Joris Gansemans|
VIB (the Flanders Institute for Biotechnology)