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 Radioisotope couple for tumor diagnosis and therapy
14.05.2019 | Kanazawa University

nachricht Therapy Optimisation by Analysing the Genome
13.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

Im Focus: A step towards probabilistic computing

Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future

When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...

Im Focus: Recording embryonic development

Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells

The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Discovering unusual structures from exception using big data and machine learning techniques

17.05.2019 | Materials Sciences

ALMA discovers aluminum around young star

17.05.2019 | Physics and Astronomy

A new iron-based superconductor stabilized by inter-block charger transfer

17.05.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>