Protein pulling -- Learning how proteins fold by pulling them apart

Jul 19, 2007

Rice University physicists have unveiled an innovative way of finding out how proteins get their shape based on how they unfold when pulled apart. The experimental method could be of widespread use in the field of protein folding science, which has grown dramatically in the past decade, due in part to the discovery that misfolded proteins play a key role in diseases like Alzheimer's and Parkinson's.

Rice's new findings, which were three years in the making, are available online and slated to appear in an upcoming issue of Physical Review Letters. The article describes a new method scientists can use to map out exactly how much free energy is required throughout the folding process.

"We believe the method can be applied to any protein," said lead author Ching-Hwa Kiang, assistant professor of physics and astronomy. "Many people are working on this problem, and when we present our work at scientific conferences it often creates a good deal of excitement."

If DNA is the blueprint for life, then proteins are the machines built from those blueprints. All living cells produce proteins by stringing together strands of amino acids based on the sequences of their DNA. Proteins are created in linear chains, like strands of pearls, with each amino acid representing a bead on the strand. However, knowing the order of the amino acids in the strand gives no clue about how a protein functions. That's because every protein folds into a three-dimensional shape within about one second of being made, and it is this shape that dictates the protein's function.

By studying how much free energy it takes for a protein to fold into its final shape, scientists hope to learn more about how amino acid sequences affect protein function and how folding goes awry, as with some diseases.

At the halfway point between it's folded and unfolded state, a protein is like a rollercoaster balanced at the crest of the highest hill on the track. Like the rollercoaster, the protein requires a certain amount of energy to make it over the hill and wind its course to a final resting place -- its folded state. If it lacks the energy to clear the hill, it will slide back into a partially folded or misfolded state.

Kiang and graduate student Nolan Harris's new approach to probing these energy states yields something akin to a map of the rollercoaster's path. For example, theirs is the only experimental method that can reveal the slope and height of the energy barrier that the protein must overcome.

"Other experimental methods give researchers a pretty clear picture of the energy states at the beginning and the end -- the two equilibrium states," Kiang said. "Our approach helps fill in what happens in between, when the system is between folded and unfolded."

Kiang and Harris's experiments were conducted on one piece of a protein named Titin. The Titin piece, dubbed I27, contains 89 amino acids. Harris suspended thousands of intact, folded I27s in a dilute saline solution and let the solution sit long enough for the proteins to become stuck to the bottom of the sample dish. The needle from an atomic force microscope (AFM) was repeatedly dipped into the solution. The tip of the AFM operates much like a phonograph needle. The AFM needle is on the end of a cantilever arm that bobs up and down over the sample. The tip of the AFM needle is just a few atoms wide. Bobbing down, it randomly grabbed I27s that were pulled into their string-like, unfolded shape as the needle rose.

Harris measured the force exerted on the cantilever arm each time an I27 was unfolded. To get the energy maps, he wrote software incorporating a statistical mechanics equation called the "Jarzynski equality." The equation related the non-equilibrium energy from the unfolding events to the equilibrium profiles along the trajectory from the folded to the unfolded state. Kiang said the software, and the use of the Jarzynski equality, makes the new method unique and useful.

"Christopher Jarzynski only discovered this relationship 10 years ago," Kiang said. "It's a very powerful technique."

Source: Rice University

Explore further: Engineering discovery brings invisibility closer to reality

add to favorites email to friend print save as pdf

Related Stories

A contractile gel that stores light energy

Jan 20, 2015

Living systems have the ability to produce collective molecular motions that have an effect at the macroscale, such as a muscle that contracts via the concerted action of protein motors. In order to reproduce ...

Study uncovers secrets of a clump-dissolving protein

Jan 22, 2015

Workhorse molecules called heat-shock proteins contribute to refolding proteins that were once misfolded and clumped, causing such disorders as Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's ...

Scientists set quantum speed limit

Jan 22, 2015

University of California, Berkeley, scientists have proved a fundamental relationship between energy and time that sets a "quantum speed limit" on processes ranging from quantum computing and tunneling to ...

Sonic booms in nerves and lipid membranes

Jan 20, 2015

(Phys.org)—Neurons might not be able to send signals as fast as electrons in wires or photons in fiber, but what if they can communicate using miniature sonic booms? That would be quite a revolutionary ...

Recommended for you

Infrared imaging technique operates at high temperatures

Jan 23, 2015

From aerial surveillance to cancer detection, mid-wavelength infrared (MWIR) radiation has a wide range of applications. And as the uses for high-sensitivity, high-resolution imaging continue to expand, MWIR sources are becoming ...

Football physics and the science of Deflategate

Jan 23, 2015

News reports say that 11 of the 12 game balls used by the New England Patriots in their AFC championship game against the Indianapolis Colts were deflated, showing about 2 pounds per square inch (psi) less ...

Physicists find a new way to slow the speed of light

Jan 23, 2015

(Phys.org)—A team of physicists working at the University of Glasgow has found a way to slow the speed of light that does not involve running it through a medium such as glass or water. Instead, as they ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.