Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure of key receptor unlocked; Related proteins will fall like dominoes

06.08.2002


After two years of stubborn persistence, scientists at Johns Hopkins have determined the 3-D structure of part of a protein called HER3, which should speed efforts to interfere with abnormal growth and cancer.



"It took us more than two years to interpret the data and get HER3’s structure," says Dan Leahy, Ph.D., a Howard Hughes Medical Institute investigator and a professor of biophysics in Hopkins’ Institute for Basic Biomedical Sciences. "Now that we have it, it might take only weeks to figure out its relatives."

Reporting the structure in the Aug. 1 online version of Science, Leahy says finding out the shapes of the entire HER family of proteins, HER1, HER2 and HER4, will provide the first opportunity to rationally design new drugs to interfere with them, possibly preventing or treating select forms of cancer.


HER2, for example, is the target of the breast cancer treatment Herceptin, an antibody. But while it’s an effective life-prolonging treatment in certain breast cancer patients, different strategies targeting HER2 might also prove effective. Having a protein’s structure allows scientists to conceive new strategies and pursue new classes of drugs, says Leahy.

A focus of many scientists because of the proteins’ involvement in cell growth, the HER family are receptors for "epidermal growth factor" (EGF) and other chemicals. Although the DNA sequences of HER proteins have been known for some time, technical problems dogged efforts to understand how the proteins are shaped, Leahy says.

"Until we know proteins’ structures, we’re very limited in figuring out how a molecule or possible drug might bind," says Leahy. "We now have a starting point to see how molecules binding to HER3 change its shape and turn it on."

Stuck in the cell membrane, each HER protein consists of three parts: a region outside the cell that recognizes and binds certain molecules; a region that anchors the protein in the cell membrane; and a region inside the cell that, when activated, adds phosphates to various proteins. Leahy and postdoctoral fellow Hyun-Soo Cho determined the structure of the first of these regions for HER3.

Combining a number of available methods, Leahy, Cho and technician Patti Longo purified large amounts of the HER3 receptor region and formed uniform crystals, crucial for figuring out protein structures. By bombarding the crystals with X-rays at the National Synchrotron Light Source at Brookhaven National Laboratory in New York, Cho got the information he needed to start figuring out how the protein looks in space.

In each crystal there are billions of protein molecules, organized in a careful pattern. As the X-rays travel through the crystal, they hit individual atoms in the protein and are bounced back or bent, depending on the 3-D arrangement of the atoms. Others travel through unaffected. By analyzing where the X-rays end up, the scientists can reconstruct how the protein is put together.

One unexpected aspect of the protein’s structure is what Leahy and Cho call the "snap" region -- two finger-like loops that reach out toward one another and interact, stabilizing the structure.

"While it’s all speculation right now, it’s easy to imagine how losing the "snap" interaction might be involved in binding or activation," Leahy says.

HER1 and HER4 have the same sequence of building blocks in the "snap" region, but HER2 does not, which may help explain why HER2 is the only one of the four receptors that interacts only with other HER proteins.


The experiments were funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Media Contact: Joanna Downer 410-614-5105
Email: jdowner1@jhmi.edu

Joanna Downer | EurekAlert!
Further information:
http://www.sciencemag.org/sciencexpress/recent.shtml

More articles from Life Sciences:

nachricht Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State

nachricht New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

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

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>