Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

St. Jude shows how disorderliness in some proteins lets them interact with a diversity of molecules

22.03.2004


Discovery of the sequence of events in the binding of p27 to a protein complex is a model for explaining how 30 to 40 percent of the body’s proteins exploit their flexibility in order to do different tasks in the cell



Investigators at St. Jude Children’s Research Hospital have demonstrated for the first time that--contrary to the long-held belief among scientists that proteins must maintain a rigid structure in order to perform an assigned task--many proteins actually exploit disorderliness in their structure to perform a variety of different jobs. The findings of this research appear in the current, online issue of Nature Structural and Molecular Biology.

The St. Jude finding explains how many of the body’s proteins can adapt their structures to the needs of the moment, binding to different molecules depending on the job at hand.


"The potential importance of disorder in the function of some proteins has been discussed by researchers for several years," said Richard W. Kriwacki, PhD, associate member of the St. Jude Department of Structural Biology and senior author of the report. "But until now no one had actually demonstrated how such flexibility allows a protein to interact with different molecules. We’ve taken a big step in understanding the subtle details of a critical biochemical process in the life of the cell."

Previously, other researchers suggested that 30 to 40 percent of the body’s proteins do not rely on a rigid structure to interact with target molecules. In the current study, the St. Jude team verified that idea by showing how a protein called p27 uses two flexible arms to help it bind to a protein complex called Cdk2-cyclin A. This interaction is important because Cdk2-cyclin A is one of the so-called "master timekeepers" of cell division. These timekeepers trigger sequential events leading to the production of new daughter cells. By binding to Cdk2-cyclin A and blocking its activity, p27 disrupts this sequence and prevents the cell from dividing. The importance of p27’s role in regulating cell division is highlighted by findings showing that loss of p27 function is a key contributing factor in several types of cancer.

The researchers demonstrated that the p27 protein resembles a relatively rigid helical (twisted) rod with a wobbly piece of spaghetti hanging off each end. One of the wobbly arms binds to cyclin A, while the other arm binds to Cdk2.

When p27 is by itself in a solution, the arms are loose and disordered. But when p27 encounters Cdk2-cyclin A, one of its arms binds to cyclin A by folding into a rigid shape. After the first arm binds, the center rod settles across the entire Cdk2-cyclin A complex. Finally, the second arm also folds into a rigid shape onto the Cdk2 part of the complex. In this way, proteins such as p27 act as molecular ’staples’ that fasten onto their targets.

"The very act of binding to the Cdk2-cyclin A complex makes the loose, disordered arms of p27 fold up and become rigid," Kriwacki said.

The researchers also discovered how proteins like p27 can identify and bind to complexes with different types of Cdk and cyclin, such as Cdk4-cyclin D--an ability that is critical for them to correctly identify which complexes they are supposed to regulate.

"We discovered that all Cdk molecules look pretty much alike to p27," Kriwacki said. "But a certain part of each type of cyclin is unique. The first flexible arm of p27 recognizes only certain types of cyclin, based on that unique part of the molecule. The first arm binds to this part of the cyclin, and the rest of the p27 follows along."

Using nuclear magnetic resonance spectrometry, which combines radio wave emissions and a powerful magnetic field to determine the structure of proteins suspended in solutions, the team determined the shape of p27 when it was unbound. In order to study the interaction between p27 and Cdk2-cyclin A, researchers in the St. Jude Hartwell Center for Bioinformatics and Biotechnology used a technique called surface plasma resonance. This technique measures the changes in the reflection of light off p27 before and after it binds to Cdk2-cyclin A.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/
http://www.stjuderesearch.org/data/kriwackilab/p27movie.mpg

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>