Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Changes in shape of single protein plays key role in the spread of cancer cells

07.01.2004


Milestone discovery of the 3-D structure and function of vinculin explains how this protein changes its shape to perform different functions in health and disease



The discovery of how a protein called vinculin undergoes exquisitely precise changes in its shape is helping to answer some major questions about the life of cells, the development of tissues and organs and the spread of cancer from one part of the body to another. These findings, to be published in the Jan. 8, 2004, issue of Nature, were made by scientists at St. Jude Children’s Research Hospital.

The newly recognized way that this protein can change its shape is important because slight changes in the shape of vinculin completely change its role in the cell, making the protein a versatile tool for completing different tasks. For example, by alternately changing its shape from active to inactive forms, vinculin can control the cell’s ability to remain stationary or move through its environment.


Vinculin enables cells to move within developing tissues and organs of the embryo and spark the healing of wounds. But vinculin can also regulate the ability of cancer cells to move away from tumors and spread cancer to other parts of the body, according to Tina Izard, Ph.D., assistant member in the Department of Hematology-Oncology. Izard led the research team and is the first and senior author of a report on this work.

The discovery of how vinculin changes its shape holds promise for developing new ways to prevent the spread of cancer cells. The milestone discoveries of changes in the shape and function of vinculin illustrate the versatility of some proteins and help explain how the enormous complexity of the human body can arise from a mere 30,000 to 40,000 genes, according to Philippe R.J. Bois, Ph.D., a Van Vleet Foundation fellow in the St. Jude Department of Genetics.

"It was already known that cells can read certain genes in different ways to make different proteins," Bois said. "But these new findings significantly enhance our appreciation of the scope of protein function in the cell."

The researchers used X-ray crystallography to generate information on the shape of vinculin in its inactive and active forms. Izard’s team shot X-rays at crystalline forms of human vinculin and collected the patterns formed when the X-rays diffracted off the different parts of the protein. The researchers created these patterns using the X-ray crystallography facility at the Argonne National Laboratory (Argonne, Ill.). Diffraction patterns form when X-rays are diffracted by a crystal. The vinculin diffraction patterns underwent computer processing using software developed at Global Phasing Limited, a company in Cambridge, England.

Vinculin’s ability to alter its shape to meet the demands of a task stems from the series of gracefully curling segments--each one of which is called a helix---that makes up much of the structure of this protein.

"Vinculin resembles a series of cylinders held together by threads," Izard said.

Vinculin changes its shape by moving the individual helical "cylinders" making up its head–much like the movement of the fingers on a hand--in a process called helical bundle conversion. This process, which the team discovered, occurs after one of two different proteins binds to the head.

The team demonstrated that when a protein called talin binds to vinculin’s head, the head undergoes helical bundle conversion and the helices assume new positions relative to each other, according to Izard. The new shape of the head is critical to vinculin’s ability to help the cell anchor itself to the environment outside its membrane--an area called the "extracellular matrix." This keeps the cell in one spot so it does not drift away.

However, when the protein called á-actinin (alpha-actinin) binds to vinculin’s head, the head acquires a different shape. In this shape, vinculin plays a critical role in stabilizing a chain of molecules called cadherin. This extends through the cell membrane and binds with cadherin chains from neighboring cells. The connection, similar to a chain-linked fence, permits cells to bind together into sheets, and thus form tissues and organs.

Together, talin and á-actinin help vinculin build tissues and organs out of individual cells by keeping cells in one spot.

"But when vinculin shifts from active to inactive form and back again, the cell can perform other tasks as well," Izard said. For example, such a shift lets many cells move from their original location to take up positions elsewhere in the developing body where new tissues and organs are destined to arise.

"In other words, vinculin is a critical protein that performs different roles in the body," Boise said. "It is a master conductor of much of the cell’s life, changing its shape to conduct the cell’s business according to the cell’s immediate needs."

Other authors of the study include Robert A. Borgon and Christina L. Rush (St. Jude and the University of Tennessee) and Gwyndaf Evans and Gerard Bricogne (Global Phasing Limited, Cambridge, England).



This work was supported in part by the Cancer Center Support (CORE) Grant and ALSAC.

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>