(Press-News.org) New research sheds light on the interaction between the semi-flexible protein tropomyosin and actin thin filaments. The study, published by Cell Press on February 15th in the Biophysical Journal, provides the first detailed atomic model of tropomyosin bound to actin and significantly advances the understanding of the dynamic relationship between these key cellular proteins.
Tropomyosin is a long protein that associates with actin, a highly conserved thin filament protein found in organisms from yeast to humans. Actin, a major part of the cell's cytoskeleton, drives shape changes and cellular locomotion in many types of cells, and is part of the contractile apparatus in muscle cells. Tropomyosin binds to actin ad acts as a molecular barrier, essentially covering up active sites that are required for actin to interact with other proteins. In turn cellular signals can trigger additional regulatory proteins to move tropomyosin, dislodging the barrier in order to allow actin to associate with remodeling and motor proteins.
"Previous studies examining tropomyosin in isolation suggested that it is a coiled coil that matches the shape of actin filaments and is arranged along their surface," explains senior study author, Dr. William Lehman from the Department of Physiology and Biophysics at Boston University School of Medicine. "However, a complete elucidation of tropomyosin-based regulatory mechanisms requires a complete representation of the atomic structure and mechanical properties of the tropomyosin molecule linked to its biological substrate."
Building on previous findings that the association between tropomyosin and actin is an electrostatic attraction between oppositely charged amino acids, Dr. Lehman and colleagues explored thousands of combinations of different rotations and positions of tropomyosin to find the most favorable interaction between tropomyosin and actin. The researchers then used electron microscopy as a second approach to also reconstruct the interaction. The two methods yielded virtually identical solutions, "which is very gratifying", says Dr. Lehman.
The authors discuss how the interaction between tropomyosin and actin is just weak enough that tropomyosin can be readily perturbed by regulatory proteins and act as a molecular switch to regulate actin interaction with other proteins. "The atomic model that we propose can serve as a reference location to characterize tropomyosin regulatory movements on actin thin filaments," concludes Dr. Lehman. "Moreover, the map of actin-tropomyosin provides a structural platform to assess mutations that influence actin-tropomyosin behavior and also to develop tropomyosin-mimicking peptide drugs designed to modulate actin-myosin or other interactions."
### END
Atomic model of tropomyosin bound to actin
2011-02-16
ELSE PRESS RELEASES FROM THIS DATE:
A mental retardation gene provides insights into brain formation
2011-02-16
VIDEO:
This movie shows a typical (wild type) mouse as it spends much more time exploring an object it has never seen before and little time with the object it has...
Click here for more information.
DURHAM, N.C. – Scientists at Duke University Medical Center have uncovered clues to memory and learning by exploring the function of a single gene that governs how neurons form new connections. The finding may also provide insights into a form of human mental retardation.
In a ...
Jefferson researchers provide genetic evidence that antioxidants can help treat cancer
2011-02-16
PHILADELPHIA—Researchers from Jefferson's Kimmel Cancer Center have genetic evidence suggesting the antioxidant drugs currently used to treat lung disease, malaria and even the common cold can also help prevent and treat cancers because they fight against mitochondrial oxidative stress—a culprit in driving tumor growth.
For the first time, the researchers show that loss of the tumor suppressor protein Caveolin-1 (Cav-1) induces mitochondrial oxidative stress in the stromal micro-environment, a process that fuels cancer cells in most common types of breast cancer.
"Now ...
Study finds racial disparities in hospital readmission rates
2011-02-16
Elderly Medicare black patients have a higher 30-day hospital readmission rate for several conditions including congestive heart failure and pneumonia compared to white patients, that is related in part to higher readmission rates among hospitals that disproportionately care for black patients, according to a study in the February 16 issue of JAMA.
"Racial disparities in health care are well documented, and eliminating them remains a national priority. Reducing readmissions has become a policy focus because it represents an opportunity to simultaneously improve quality ...
Higher levels of compound in blood associated with lower risk of respiratory disease
2011-02-16
An analysis of data including more than 500,000 adults indicates that levels in the blood of bilirubin (a compound produced by the breakdown of hemoglobin from red blood cells) in the normal range but relatively higher were associated with a reduced risk of lung cancer, chronic obstructive pulmonary disease and all-cause death, according to a study in the February 16 issue of JAMA.
Serum total bilirubin is routinely measured in the primary care setting to identify hepatobiliary (liver, gall bladder and bile ducts) and blood diseases. Bilirubin may have cytoprotective ...
Large portion of costs at children's hospitals accounted for by patients with frequent readmissions
2011-02-16
Among a group of children's hospitals, nearly 20 percent of admissions and one-quarter of inpatient expenditures were accounted for by a small percentage of patients who have frequent recurrent admissions, according to a study in the February 16 issue of JAMA.
Hospital readmission is increasingly considered an indicator of quality of care. Some children with chronic illnesses may be readmitted on a recurrent basis, but there are limited data regarding the impact of their rehospitalizations, according to background information in the article. "Children with chronic conditions ...
Method of DNA repair linked to higher likelihood of genetic mutation
2011-02-16
Accurate transmission of genetic information requires the precise replication of DNA. Errors in DNA replication are common and nature has developed several cellular mechanisms for repairing these mistakes. Mutations, which can be deleterious (development of cancerous cells), or beneficial (evolutionary adaption), arise from uncorrected errors. Researchers from Indiana University-Purdue University Indianapolis (U.S.A) and Umea° University (Sweden) report that a method by which cells repair breaks in their DNA, known as Break-induced Replication (BIR), is up to 2,800 times ...
Zinc reduces the burden of the common cold
2011-02-16
Zinc supplements reduce the severity and duration of illness caused by the common cold, according to a systematic review published in The Cochrane Library. The findings could help reduce the amount of time lost from work and school due to colds.
The common cold places a heavy burden on society, accounting for approximately 40% of time taken off work and millions of days of school missed by children each year. The idea that zinc might be effective against the common cold came from a study carried out in 1984, which showed that zinc lozenges could reduce how long symptoms ...
Safety of biologic treatment for arthritis depends on the drug
2011-02-16
Some biologic drugs may be safer than others according to a new systematic review by Cochrane researchers. Biologics are a broad class of drugs based on biological molecules. The drugs are used to reduce inflammation in diseases such as rheumatoid arthritis and inflammatory bowel disease.
Although the effectiveness of biologics is now well established, it is thought that some may have rare but serious side effects related to their immune-suppressing activities. Links have been made to increased risk of infections, reactivation of tuberculosis (TB), cancer and congestive ...
Tick population plummets in absence of lizard hosts
2011-02-16
Berkeley — The Western fence lizard's reputation for helping to reduce the threat of Lyme disease is in jeopardy. A new study led by researchers at the University of California, Berkeley, found that areas where the lizard had been removed saw a subsequent drop in the population of the ticks that transmit Lyme disease.
"Our expectation going into this study was that removing the lizards would increase the risk of Lyme disease, so we were surprised by these findings," said study lead author Andrea Swei, who conducted the study while she was a Ph.D. student in integrative ...
Study finds blacks more likely to be readmitted to hospitals after discharge
2011-02-16
Boston, MA – Elderly black patients were more likely to be readmitted to the hospital after a prior hospital stay for a heart attack, heart failure, or pneumonia, according to a new study from Harvard School of Public Health (HSPH) researchers. They found that the higher readmission rates were due to disparities related to both race and the hospitals where patients were treated.
"Disparities in health and health care are well-documented in this country, but little was previously known about whether there were disparities in hospital readmissions at the national level," ...