Flemish researchers provide the first experimental evidence of dynamic allostery in protein regulation

Jul 09, 2010

The brand-new Jean Jeener Bio-NMR Center at the VIB Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel, has already played a role in a scientific breakthrough that made it into the leading science journal Cell. Thanks to NMR technology, it is possible to determine the dynamic structure of proteins. So Flemish scientists put it to use to find out how the activity of certain proteins involved in the stress physiology of bacteria is regulated. This is a first in every way.

Proteins play a major role in the billions of processes that occur in the body, including the development of muscle and skin, the digestion of food, the growth of cells and the generation of human emotions. Our cells continuously produce proteins, but how these complex molecules exactly function is by and large not well understood.

Not only the but also the spatial structure of proteins is important for the performance of their functions. The ways in which they fold and unfold in three-dimensional space help determine the function of the molecules. So, without detailed knowledge about their structure, our understanding of their function usually remains partial. However, studying the spatial structure of proteins is anything but easy.

NMR is a promising technique for determining the structure of proteins in solution. Unlike X-ray diffraction - long the standard for determining the structure of proteins - NMR equipment can provide dynamic structure information. Even vibrations and rotations of molecules on an can be visualized. The Bio-NMR center at the VIB Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel, only opened May 7, 2010, but its 600-MHz and 800-MHz spectrometers have already helped produce a first article in a top journal.

Regulation of 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 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.

Explore further: Do sexually transmitted diseases drive variation in mammalian immunity?

Provided by Flanders Institute for Biotechnology

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

Bacteria pack their own demise

Jul 30, 2009

Numerous pathogens contain an 'internal time bomb', a deadly mechanism that can be used against them. After years of work, VIB researchers at the Vrije Universiteit Brussel (VUB) were able to determine the structure and operating ...

First NMR Signal of a Copper Site in Azurin Obtained

Feb 18, 2010

(PhysOrg.com) -- Metalloproteins, such as the copper-containing azurin, play a major role in catalyzing electron transfer in cellular reactions. Understanding how their structure relates to function can give ...

Recommended for you

How malaria-spreading mosquitoes can tell you're home

Jan 22, 2015

Females of the malaria-spreading mosquito tend to obtain their blood meals within human dwellings. Indeed, this mosquito, Anopheles gambiae, spends much of its adult life indoors where it is constantly expose ...

Study uncovers secrets of a clump-dissolving protein

Jan 22, 2015

Workhorse molecules called heat-shock proteins contribute to refolding proteins that were once misfolded and clumped, causing such disorders as Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's ...

Using viruses to find the cellular Achilles heel

Jan 22, 2015

Back-to-back studies from researchers at the Gladstone Institutes have exposed new battle tactics employed by two deadly viruses: hepatitis C (HCV) and the Kaposi's sarcoma-associated herpesvirus (KSHV). Published in the ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.