Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Discover Mutation Causing Protein Misfolding Remission

12.05.2010
Light chain amyloidosis, a deadly protein misfolding disease, is caused by multiple mutations in cells that are intended to protect the body.

Instead, the mutations send misfolded bundles of proteins through the bloodstream, potentially destroying the heart, kidneys, liver or other organs. Mayo Clinic researchers have identified one of these mutations and have shown that the molecule’s shifting position is as important as its unique shape. The findings appear in the current issue of the journal Structure.

“This is a condition that often is misdiagnosed because it could appear as many other common conditions and can affect different organs,” says Marina Ramirez-Alvarado, Ph.D., Mayo Clinic biochemist and senior author of the study. “It can be initially identified by a simple blood test and a fat aspirate analysis. After that, we can only treat symptoms as there is currently no cure.”

About 2,000 patients are diagnosed with amyloidosis annually in the United States. Survival after diagnosis averages about three years. Immunoglobulin molecules made in cells from the bone marrow are subject to mutations that can cause the proteins to misfold. In essence, what should be a set configuration of amino acids becomes chaotic, appearing in models as a twisted ball of “spaghetti” that then accumulates more fibrous threads called fibrils. These misfolded proteins travel in the bloodstream accumulating fibrils that clog osmotic and other filtering processes in the liver, kidneys and heart, ultimately causing other organ-based diseases.

Mayo researchers studied light chains that normally are made in plasma B cells as part of the protective immune mechanism, found in bone marrow. Through a combination of crystallography, nuclear magnetic resonance spectroscopy, and bioinformatics, they were able to determine the surface shape of the molecule involved with one mutation and also deduce that it was constantly shifting its position, from 90 degrees to 180 degrees off the normal position of the comparable functional protein.

Because of the realignment, the protective nature of the molecule is lost and its new molecular contacts promote amyloid formation. This process is what happens in 85 percent of amyloidosis patients. In this specific case, the researchers were able to identify that the mutation called the Tyr-to-His substitution in the reconfiguration at position 87 on the protein was the alteration that promoted fibril development. Researchers say that while this is just one of many possible mutations, it is a beginning towards identifying targets for future drug development in a condition that is otherwise fatal.

Others involved in the study are Elizabeth Baden, Ph.D., and Barbara Owen, Ph.D., Mayo Clinic; Francis Peterson, Ph.D., and Brian Volkman, Ph.D., both of the Medical College of Wisconsin, Milwaukee. The National Institutes of Health and Mayo Clinic supported the research.

About Mayo Clinic
For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic’s campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your general health information.

Robert Nellis | Newswise Science News
Further information:
http://www.mayo.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>