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 The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>