Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Spiders Help Scientists Discover How Muscles Relax

25.08.2005


Using muscle tissue from tarantulas, an HHMI international research scholar and his colleagues have figured out the detailed structure and arrangement of the miniature molecular motors that control movement. Their work, which takes advantage of a new technique for visualizing tissues in their natural state, provides new insights into the molecular basis of muscle relaxation, and perhaps its activation too.


Atomic Model of the Thick Filament from Tarantula Striated Muscle - The surface of the three-dimensional reconstruction of the thick filament is shown in gray, together with the atomic models of two myosin molecules, indicating the intramolecular and intermolecular interactions. Image: John Woodhead



“We have solved the structure of the array of miniature motors that form our muscles and found out how they are switched off,” said Raúl Padrón, a HHMI international research scholar in the Department of Structural Biology at the Venezuelan Institute for Scientific Research (Instituto Venezolano de Investigaciones Científicas or IVIC) in Caracas, Venezuela.

The findings are reported in the August 25, 2005, issue of the journal Nature.


Padrón and his colleagues focused their studies on striated muscle—the type of muscle that controls skeletal movement and contractions of the heart. Striated muscles are made of long cylindrical cells called muscle fibers. Within the fibers, millions of units known as sarcomeres give rise to movement of skeletal muscles. Sarcomeres are composed mainly of thick filaments of myosin, the most common protein in muscle cells, responsible for their elastic and contractile properties. The thick filaments are arranged in parallel with thin filaments of another muscle protein, actin. When the actin and myosin filaments slide along one another, the muscle contracts or relaxes.

Padrón’s study focused on the long, rod-shaped myosin of the thick filaments. The heads of these myosin rods project outward from the thick filament to connect with and move actin filaments during contraction of a muscle.

The structural studies were done using tarantula striated muscle, which the team has been studying since the 1980s. Striated muscles from the large, hairy spiders contain filaments that are particularly well ordered, making them easier to study structurally than the more disorganized filaments found in vertebrate striated muscle, Padrón explained.

Padrón and Lorenzo Alamo at IVIC partnered with Roger Craig, John Woodhead and Fa-Qing Zhao at the University of Massachusetts Medical School to use cryo-electron microscopy to answer questions about the thick filament’s structure, questions that could not be answered with existing electron microscopy techniques.

Standard electron microscopy requires dehydration and staining of a tissue sample, which modifies the structure of the specimen and distorts its shape. Cryo-electron microscopy avoids these problems by rapidly freezing the sample. Using the new technique, the researchers were able to visualize the muscle tissue in a form closer to its structure in the body than had previously been possible.

It took several years to refine the techniques required to preserve the thick muscle filaments in their relaxed state. Even then, the researchers faced mathematical difficulties in calculating a three-dimensional map of the filaments. In 2004, using a new approach that Edward Egelman at the University of Virginia Health Sciences Center had developed to create the map, they soon had their structure. “The new reconstruction was very detailed; we were all amazed with the level of detail that it showed,” Padrón said.

The structure provides crucial new details. A twisting, symmetrical arrangement of myosin heads spaced around the filament’s circumference surrounds a backbone made up of 12 parallel strands or sub-filaments. “This is the first time that the structure of the backbone has been clearly seen in any thick filament reconstruction,” the researchers wrote.

“The structure reveals how the helices of the myosin heads are formed and maintained and how the filaments are switched off due to interactions between the myosin heads Padrón explained. “It also opens the way to understanding how the thick filaments are activated.”

The details of their model permitted the researchers to explain how, in relaxed muscle, the heads of each myosin molecule are inhibited from interacting with actin by interacting with each other instead. When muscle is activated, they suggest, the bonds between the myosin heads are broken. This frees each head to interact with actin and cause muscle contraction.

“We have focused on the relaxed muscle to understand the structure of the thick filaments when they are not involved in contraction, but rather fully ordered—a state more amenable to understanding their structure,” Padrón said. “Solving the structure of the relaxed state will allow us to investigate how these filaments are activated when they are switched on.”

The scientists were surprised to find that the atomic structure of isolated myosin molecules from vertebrate smooth muscle—the type of muscle found in the digestive tract, bladder, arteries, and veins—closely matched their invertebrate striated muscle myosin filament. Kenneth Taylor’s research group at Florida State University reported the atomic structure of the smooth muscle myosin molecules.

The similarity suggests, Padrón said, that the interacting head structure may be common to relaxed-state myosin for smooth and striated muscle and among varied species. “This model is applicable across the whole animal kingdom and all muscle types, and that’s exciting,” he remarked.

Padrón said he hopes to apply the research to muscle diseases that arise from malfunctioning of the muscles’ on/off switches. One such disease is hypertrophic cardiomyopathy, in which the wall of the left ventricle of the heart becomes enlarged, causing sudden death. It is caused by mutations in certain genes that encode several muscle proteins—some of which are related specifically to the myosin that Padrón studies.

Jennifer Donovan | EurekAlert!
Further information:
http://www.hhmi.org

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 >>>