Nav: Home

Peering under the hood into the workings of molecular motors

December 21, 2015

Understanding how tiny molecular motors called myosins use energy to fuel biological tasks like contracting muscles could lead to therapies for muscle diseases and cancers, says a team of researchers led by Penn State College of Medicine scientists.

Myosins are proteins that use high-energy adenosine triphosphate, or ATP, to accomplish mechanical work such as muscle contractions, cell motility and cell division.

In muscles, myosins generate movement by interacting with actin filaments, a fibrous track they can bind to and move along. The proteins produce motion in a mechanical step known as the power stroke.

Scientists are interested in the timing of the movement of myosin along actin filaments which is driven by the power stroke -- a process called lever arm swing. Although they knew that myosin splits ATP into its products -- phosphate and ADP -- during this process, the precise timing and sequence of these events has been unclear.

"There are millions of myosin molecules in a muscle fiber and each one individually generates a displacement," said Christopher M. Yengo, associate professor of cellular and molecular physiology. "Collectively, myosins generate a large amount of force to contract muscle. The question has always been: How does this actually work? How can these little motor proteins generate these tiny displacements?"

To investigate, the researchers needed to watch force generation happen in real time. They attached fluorescent probes to parts of the myosin motor and observed distance changes between the glowing probe sites to time the protein's force-generating movements.

They found two steps in the process: a fast step that occurs before phosphate release and a slow step prior to ADP release.

"In our study, we learned that the lever arm swing 'gates' the release of phosphate," Yengo said. "This means that myosin is extremely efficient because it only proceeds through the ATP hydrolysis cycle when it generates force and motion," Yengo said. The findings were published in the Proceedings of the National Academy of Sciences.

These insights provide details about how myosin motor proteins work, and this knowledge could advance the understanding of diseases related to movement on a molecular level.

Myosin has been implicated in certain types of congenital and delayed-onset deafness. The protein plays a role in the detection of sound waves in the inner ear. A better understanding of how myosin helps cells move and divide could even stop cancer in its tracks, Yengo said. A drug that prevents myosin from working in cancer cells could keep them from invading other cells or metastasize into different organs.

Muscle diseases are the major area of interest for myosin researchers. For example, myosin mutations are believed to be behind an inherited disease that causes the walls of the heart muscle to become too thick or too thin. An error in the timing of force generation in the heart could explain the condition.

"By knowing that information we can design drugs to correct the defect that's caused by the mutation," Yengo said.
-end-
Other investigators on this project were Darshan V. Trivedi and Anja M. Swenson from the Department of Cellular and Molecular Physiology, Penn State College of Medicine; Joseph M. Muretta and David D. Thomas, University of Minnesota; and Jonathan P. Davis, The Ohio State University. The American Heart Association supported this work.

Penn State

Related Proteins Articles:

Discovering, counting, cataloguing proteins
Scientists describe a well-defined mitochondrial proteome in baker's yeast.
Interrogating proteins
Scientists from the University of Bristol have designed a new protein structure, and are using it to understand how protein structures are stabilized.
Ancient proteins studied in detail
How did protein interactions arise and how have they developed?
What can we learn from dinosaur proteins?
Researchers recently confirmed it is possible to extract proteins from 80-million-year-old dinosaur bones.
Relocation of proteins with a new nanobody tool
Researchers at the Biozentrum of the University of Basel have developed a new method by which proteins can be transported to a new location in a cell.
Proteins that can take the heat
Ancient proteins may offer clues on how to engineer proteins that can withstand the high temperatures required in industrial applications, according to new research published in the Proceedings of the National Academy of Sciences.
Designer proteins fold DNA
Florian Praetorius and Professor Hendrik Dietz of the Technical University of Munich have developed a new method that can be used to construct custom hybrid structures using DNA and proteins.
The proteins that domesticated our genomes
EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human genome.
Rare proteins collapse earlier
Some organisms are able to survive in hot springs, while others can only live at mild temperatures because their proteins aren't able to withstand such extreme heat.
How proteins reshape cell membranes
Small 'bubbles' frequently form on membranes of cells and are taken up into their interior.

Related Proteins Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...