Heat shock proteins ram into other proteins, generating force that is beneficial
Studies at The University of Texas Health Science Center at San Antonio are providing basic new understanding about "heat shock proteins," also called "chaperone proteins." These proteins, first identified in cells subjected to heat, are very important under many stressful and non-stressful metabolic conditions.
They maintain proper protein function and, importantly, prevent the inappropriate accumulation of damaged proteins. For example, accumulation of damaged proteins such as beta amyloid, tau and synuclein are thought to be very important in the development of diseases of the brain such as Alzheimer's disease and Parkinson's disease.
Aug. 1 in the journal Nature Structural & Molecular Biology, a Health Science Center research team led by Rui Sousa, Ph.D., and Eileen M. Lafer, Ph.D., both professors of biochemistry in the School of Medicine, presented data that show how heat shock proteins break apart protein complexes. They found that when heat shock proteins with molecular weight 70 (Hsp70s) are recruited to protein complexes, rather than simply binding to these complexes, the Hsp70s collide with them and generate a force that dissolves the complexes.
"No one knew how the heat shock proteins pull apart bad protein complexes," Dr. Sousa said. "At the molecular level, everything is moving, colliding and bumping, and smashing into other components of the cells. We found that the system moves Hsp70s to where they are needed. Once this occurs, collision pressures pull things apart."
Previous attempts to glean this information failed because the proteins studied were too heterogeneous--of too many different sizes, shapes and actions--to isolate the Hsp70 behavior.
The UT Health Science Center team studied clathrin, a protein that is uniform in size and shape and is important in making intracellular cages that transport other proteins. Previously clathrin was only available from animal specimens, making it very difficult to manipulate experimentally. Dr. Lafer made a technical breakthrough when she was able to grow clathrin in bacteria for the first time using recombinant DNA technology. The clathrin could then be genetically engineered for mechanistic studies.
Dr. Lafer grew clathrin "cages"--shaped like microscopic soccer balls--that provided the biological raw material for Dr. Sousa and the team to study the force that occurs with Hsp70 collisions. The clathrin model system could be manipulated to yield precise results.
A wrecking machine
Dr. Sousa gave this analogy of the study: The heat shock protein is like a worker with an ax who, when moved to a wood pile, begins swinging. The wood pile represents a protein complex. The scientists give the worker both thick trees and thin trees to swing at, and spindly wood and hard wood. They change the angle of the wood pile, and every other variable, to learn how this affects the chopping.
By making variants of clathrin with recombinant DNA technology, team members were able to manipulate this biological material in ways that allowed them to determine the mechanism by which it is taken apart by Hsp70.
"This work was a tour de force, requiring the convergence of exceptional biochemical and molecular genetic skills with a deep understanding of the principles of physical chemistry," said Bruce Nicholson, Ph.D., chair of the Department of Biochemistry at the Health Science Center. "Such insights into the most basic aspects of protein chemistry and cell biology are often, as in this case, driven by a curiosity to find out how the molecular machines that drive our bodies work. But from these basic pursuits of scientific curiosity will often stem great benefits to human health."
Hsp70 in disease
Understanding Hsp70 behavior may have relevance to human disease. By increasing Hsp70 function, scientists cured Huntington's, a neurodegenerative disease, in a fly model. Cancer is another interesting focus. Tumors rely on Hsp70s to survive, so lowering Hsp70 function is a topic in cancer research.
"This is an impressive study that not only improves our understanding of cellular biology, but could lead to therapeutic discoveries for neurodegenerative diseases," said Francisco González-Scarano, M.D., dean of the School of Medicine and executive vice president for medical affairs of the Health Science Center. "It is a tribute to scientists who ask hard questions and develop tools to answer them. My congratulations to the team."
"We attacked this problem because it was a really important question in cellular biology," Dr. Lafer said. "We didn't do it because we wanted to cure neurodegenerative disease or cancer. We know, however, that when we attack really important questions in science and biology, it ultimately leads to translational applications down the line."
"Sometimes as a scientist you just increase understanding of the way the world works," Dr. Sousa said. "This is something scientists have wanted to know."
About the UT Health Science Center at San Antonio
The University of Texas Health Science Center at San Antonio, with missions of teaching, research and healing, is one of the country's leading health sciences universities. Its schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced 33,000 alumni who are advancing their fields throughout the world. With six campuses in San Antonio and Laredo, the university has a FY 16 revenue operating budget of $801.8 million and is the primary driver of its community's $30.6 billion biomedical and health care industry. For more information on the many ways "We make lives better®," visit http://www.
Will Sansom | EurekAlert!
Researchers reveal new details on aged brain, Alzheimer's and dementia
21.11.2017 | Allen Institute
Nanoparticles help with malaria diagnosis – new rapid test in development
21.11.2017 | Fraunhofer-Institut für Silicatforschung ISC
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Materials Sciences
21.11.2017 | Health and Medicine