PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

RUB researchers clarify catalysis mechanism of cell growth protein Ras

PNAS: Proteins bring tension to the phosphate chain

2012-09-18
(Press-News.org) Proteins accelerate certain chemical reactions in cells by several orders of magnitude. The molecular mechanism by which the Ras protein accelerates the cleavage of the molecule GTP and thus slows cell growth is described by biophysicists at the Ruhr-Universität Bochum led by Prof. Dr. Klaus Gerwert in the Online Early Edition of the journal PNAS. Using a combination of infrared spectroscopy and computer simulations, they showed that Ras puts a phosphate chain under tension to such an extent that a phosphate group can very easily detach - the brake for cell growth. Mutated Ras is involved in tumour formation, because this reaction slows down and the brake for cell growth fails. "Our findings could help to develop small molecules that restore the Ras proteins to the right speed", says Prof. Gerwert. "Such molecules would then be interesting for molecular cancer therapy."

On/off: the Ras code

The Ras protein switches the cell growth off by detaching a phosphate group from the small bound guanosine triphosphate, GTP for short. GTP has three interlinked phosphate groups. If it is present in water, the third phosphate group can split off spontaneously - even without the help of the protein Ras. This process is very slow though. Ras accelerates the splitting by a magnitude of five, a second protein, called GAP, by a further magnitude of five. What causes this acceleration has now been found out by the Bochum team.

How Ras spans the phosphate chain

Ras brings the chain of three phosphate groups at the GTP into a certain shape. It turns the third and second phosphate group to each other so that the chain is tensioned. "Like winding up a spring in a toy car by turning a screw", explains Prof. Gerwert. "Ras is the screw, the phosphate groups form the spring." The protein GAP tensions the spring further by also turning the first phosphate group against the second. In this way, the GTP gets into such a high-energy state that the third phosphate group can easily detach from the chain - like when the toy car drives off spontaneously after winding up the spring.

Infrared spectroscopy: high resolution, but only to be interpreted indirectly

The results were obtained by the Bochum researchers using the time-resolved fourier transform infrared spectroscopy (FTIR) developed at the Institute of Biophysics. With this technique, the scientists track reactions and interactions of proteins with high spatial and temporal resolution; much more precisely than using a microscope. "However, the spectroscopy does not deliver such nice pictures as a microscope, but only very complex infrared spectra", explains PD Dr. Carsten Kötting. "Like a secret code that has to be deciphered."

Quantum chemical simulations

To this end, Till Rudack simulated the protein responses on modern computing clusters and calculated the corresponding infrared spectra. Due to the enormous computational effort, large molecules such as a complete protein cannot currently be reliably described using these so-called quantum mechanical simulations. Therefore, the researchers limited their analysis to GTP and the part of the Ras or GAP protein that interacts directly with GTP. They described the rest of the proteins with a less elaborate molecular dynamics simulation. "When bringing together all the different simulations, it is easy to be led astray", says Till Rudack. "Therefore you have to check the quality of the results by comparing the simulated with the measured infrared spectra." If the spectra obtained with both techniques match, the structure of proteins can be determined to an accuracy of a millionth of a micrometre. This was the case in the Bochum study.

Potential uses for cancer therapy

Molecular cancer therapy is already used successfully with diseases such as chronic myeloid leukaemia (CLM) in the form of the drug Gleevec. Molecules with a similar effect against the mutated Ras protein have not yet been found. "Since we are now able to investigate the reactions of the Ras protein with significantly better resolution, new hope is forming that it will be possible to defuse the mutated molecule using drugs such as Gleevec and restore the rhythm of the cell" says Gerwert.

### Bibliographic record

T. Rudack, F. Xia, J. Schlitter, C. Kötting, K. Gerwert (2012): Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations, PNAS, doi: 10.1073/pnas.1204333109

Figure online

A figure related to this press release can be found online at: http://aktuell.ruhr-uni-bochum.de/pm2012/pm00293.html.en

Further information

Prof. Dr. Klaus Gerwert, Department of Biophysics, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-24461 klaus.gerwert@bph.ruhr-uni-bochum.de

Till Rudack, Department of Biophysics, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-28363 till.rudack@bph.ruhr-uni-bochum.de

Click for more

Department of Biophysics http://www.bph.ruhr-uni-bochum.de/index_en.htm

Freely available article http://www.pnas.org/content/early/2012/08/27/1204333109.abstract

Editor: Dr. Julia Weiler


ELSE PRESS RELEASES FROM THIS DATE:

New research presents most extensive pictures ever of an organism's DNA mutation processes

New research presents most extensive pictures ever of an organisms DNA mutation processes
2012-09-18
Biologists and informaticists at Indiana University have produced one of the most extensive pictures ever of mutation processes in the DNA sequence of an organism, elucidating important new evolutionary information about the molecular nature of mutations and how fast those heritable changes occur. By analyzing the exact genomic changes in the model prokaryote Escherichia coli that had undergone over 200,000 generations of growth in the absence of natural selective pressures, the team led by IU College of Arts and Sciences Department of Biology professor Patricia L. Foster ...

Only half of adults say schools should take action when kids bully with social isolation

2012-09-18
ANN ARBOR, Mich. – U.S. adults repeatedly rate bullying as a major health problem for U.S. children. But a new poll from the University of Michigan shows adults have different views about what bullying behaviors should prompt schools to take action. The University of Michigan C.S. Mott Children's Hospital National Poll on Children's Health recently asked a nationwide sample of adults what behaviors should be considered bullying and what behaviors should spur school officials to intervene. The vast majority of adults (95 percent) say schools should take action if a student ...

Shrinking snow depth on Arctic sea ice threatens ringed seal habitat

Shrinking snow depth on Arctic sea ice threatens ringed seal habitat
2012-09-18
As sea ice in the Arctic continues to shrink during this century, more than two thirds of the area with sufficient snow cover for ringed seals to reproduce also will disappear, challenging their survival, scientists report in a new study. The ringed seal, currently under consideration for threatened species listing, builds caves to rear its young in snow drifts on sea ice. Snow depths must be on average at least 20 centimeters, or 8 inches, to enable drifts deep enough to support the caves. "It's an absolute condition they need," said Cecilia Bitz, an associate professor ...

Sex matters: Guys recognize cars and women recognize birds best

Sex matters: Guys recognize cars and women recognize birds best
2012-09-18
Women are better than men at recognizing living things and men are better than women at recognizing vehicles. That is the unanticipated result of an analysis Vanderbilt psychologists performed on data from a series of visual recognition tasks collected in the process of developing a new standard test for expertise in object recognition. "These results aren't definitive, but they are consistent with the following story," said Gauthier. "Everyone is born with a general ability to recognize objects and the capability to get really good at it. Nearly everyone becomes expert ...

Study: Parole decisions affect rehabilitation incentives

Study: Parole decisions affect rehabilitation incentives
2012-09-18
CHAMPAIGN, Ill. — Long mandatory minimum sentences or strong limits on judicial discretion can counter-productively reduce the incentives of prison inmates to engage in rehabilitative behavior, thereby raising recidivism rates, according to published research co-written by a University of Illinois economics professor. Dan Bernhardt, the IBE Distinguished Professor of Economics at Illinois, says rehabilitation incentives are maximized when the lengths of prison sentences are neither too short, nor too long. According to the paper, inmates with short prison sentences ...

International team of physicists makes discovery about temperature in convection

International team of physicists makes discovery about temperature in convection
2012-09-18
(Santa Barbara, Calif.) –– An international team of physicists is working to ascertain more about the fundamental physical laws that are at work in a process known as convection, which occurs in a boiling pot of water as well as in the turbulent movement of the liquid outer core of the Earth. The team's new finding specifies the way that the temperature of a gas or liquid varies with the distance from a heat source during convection. The research is expected to eventually help engineers with applications such as the design of cooling systems, for instance, in nuclear power ...

UCI researchers find cause of chemotherapy resistance in melanoma

2012-09-18
Irvine, Calif., Sept. 17, 2012 — Researchers with UC Irvine's Chao Family Comprehensive Cancer Center have identified a major reason why melanoma is largely resistant to chemotherapy. UCI dermatologist Dr. Anand Ganesan and colleagues found a genetic pathway in melanoma cells that inhibits the cellular mechanism for detecting DNA damage wrought by chemotherapy, thereby building up tolerance to cancer-killing drugs. Targeting this pathway, comprising the genes RhoJ and Pak1, heralds a new approach to treating the deadly skin cancer, which claims nearly 10,000 U.S. lives ...

Summer Geoscience from GSA Bulletin

2012-09-18
Boulder, Colo., USA – GSA Bulletin papers posted online from 20 July through 14 September 2012 elaborate on geoscience from Algeria, Mexico, Spain, Turkey, Nova Scotia, Switzerland, New Mexico, and the U.S. Rocky Mountains. Topics include tectonics, mineral formation, the Moho, age dating using zircon crystals, the Code of Stratigraphic Nomenclature, atmospheric CO2, and early animal evolution. GSA Bulletin articles published ahead of print are online at http://gsabulletin.gsapubs.org/content/early/recent. Representatives of the media may obtain complimentary copies of ...

Mayo Clinic researchers identify new enzyme to fight Alzheimer's disease

2012-09-18
JACKSONVILLE, Fla. — An enzyme that could represent a powerful new tool for combating Alzheimer's disease has been discovered by researchers at Mayo Clinic in Florida. The enzyme — known as BACE2 — destroys beta-amyloid, a toxic protein fragment that litters the brains of patients who have the disease. The findings were published online Sept. 17 in the science journal Molecular Neurodegeneration. Alzheimer's disease is the most common memory disorder. It affects more that 5.5 million people in the United States. Despite the disorder's enormous financial and personal ...

Cystic fibrosis disrupts pancreas two ways in CF-related diabetes

Cystic fibrosis disrupts pancreas two ways in CF-related diabetes
2012-09-18
A new University of Iowa study suggests there are two root causes of a type of diabetes associated with cystic fibrosis (CF). The findings, which already have sparked a clinical trial, may guide development of new treatments or even help prevent diabetes in patients with CF. Almost half of patients with CF will develop diabetes by age 30 and almost one quarter will develop it in their teens. In addition to the health problems caused by high blood sugar, diabetes also worsens lung disease and increases the risk of dying for people with CF. However, the underlying cause ...

LAST 30 PRESS RELEASES:

Customized smartphone app shows promise in preventing further cognitive decline among older adults diagnosed with mild impairment

Impact of COVID-19 on education not going away, UM study finds

School of Public Health researchers receive National Academies grant to assess environmental conditions in two Houston neighborhoods

Three Speculum articles recognized with prizes

ACM A.M. Turing Award honors two researchers who led the development of cornerstone AI technology

Incarcerated people are disproportionately impacted by climate change, CU doctors say

ESA 2025 Graduate Student Policy Award Cohort Named

Insomnia, lack of sleep linked to high blood pressure in teens

Heart & stroke risks vary among Asian American, Native Hawaiian & Pacific Islander adults

Levels of select vitamins & minerals in pregnancy may be linked to lower midlife BP risk

Large study of dietary habits suggests more plant oils, less butter could lead to better health

Butter and plant-based oils intake and mortality

20% of butterflies in the U.S. have disappeared since 2000

Bacterial ‘jumping genes’ can target and control chromosome ends

Scientists identify genes that make humans and Labradors more likely to become obese

Early-life gut microbes may protect against diabetes, research in mice suggests

Study raises the possibility of a country without butterflies

Study reveals obesity gene in dogs that is relevant to human obesity studies

A rapid decline in US butterfly populations

Indigenous farming practices have shaped manioc’s genetic diversity for millennia

Controlling electrons in molecules at ultrafast timescales

Tropical forests in the Americas are struggling to keep pace with climate change

Brain mapping unlocks key Alzheimer’s insights

Clinical trial tests novel stem-cell treatment for Parkinson’s disease

Awareness of rocky mountain spotted fever saves lives

Breakthrough in noninvasive monitoring of molecular processes in deep tissue

BU researcher named rising star in endocrinology

Stressed New Yorkers can now seek care at Mount Sinai’s new resilience-focused medical practice

BU researchers uncover links between metabolism and aggressive breast cancer

Engineers took apart batteries from Tesla and China’s leading EV manufacturer to see what’s inside

[Press-News.org] RUB researchers clarify catalysis mechanism of cell growth protein Ras
PNAS: Proteins bring tension to the phosphate chain