Nanotechnology Now

Our NanoNews Digest Sponsors
Heifer International



Home > Press > Physicists Report Advance in Protein Engineering

Physicists Report Advance toward a Nanotechnology Approach to Protein Engineering

Posted on June 08, 2006

UCLA physicists report a significant step toward a new approach to protein engineering this week in the online edition, and in the July print issue, of the Journal of the American Chemical Society.

“We are learning to control proteins in a new way,” said Giovanni Zocchi, UCLA associate professor of physics and co-author of the study. Zocchi said the new approach could ultimately lead to “smart medicines that can be controlled” and could have reduced side effects. Mimicking one essential cellular control mechanism, Zocchi’s laboratory has completed an important preliminary step.

UCLA - Protein Kinase
UCLA physicists Brian Choi and Giovanni Zocchi mechanically activated enzyme complex Protein Kinase A (PKA). They controlled PKA’s regulatory subunit (green and red) through a molecular spring (light blue, right). Under tension (lower part of the figure) the spring leads to a change in the regulatory subunit which causes the catalytic subunit (purple, left) to separate, activating the enzyme.

Credit: Giovanni Zocchi/UCLA Physics.

Click on image for larger version.

Zocchi and UCLA physics graduate student Brian Choi report one representative example where the chemical mechanism by which the cell controls the function of its proteins can be effectively replaced, in vitro, by mechanical control. Specifically, they show how an enzyme complex called Protein Kinase A (PKA) – which plays a fundamental role in the cell’s signaling and metabolic pathways, and is controlled in the cell by a ubiquitous messenger molecule called cyclic AMP – can instead be controlled mechanically by a nanodevice which the researchers attached to the enzyme complex. The nanodevice is essentially a molecular spring made of DNA.

“Molecular biologists have been trained for 50 years to think that because the sequence of amino acids determines a protein’s structure and the structure determines its function, if you want to change the structure, the way to do so is to change the sequence of amino acids. While that approach is correct, it is not the only way. We are introducing the notion that you can keep the sequence but change the structure with mechanical forces.

“This research has many ramifications, and may lead to a better fundamental understanding, as well as new directions for biotechnology and perhaps new approaches to medical treatments.”

PKA, a complex of four protein molecules, contains two regulatory subunits and two catalytic subunits. Zocchi and Choi mechanically activated PKA by placing a controlled mechanical stress on two specific points in the regulatory subunit, which causes that subunit to fall off from the catalytic subunit, activating the enzyme.

In order to obtain the desired effect, the mechanical tension is applied at specific locations in the regulatory subunit, Choi said. Knowing those locations requires a detailed understanding of the structure of the enzyme.

The research was federally funded by the National Science Foundation. Proteins, the molecular machines which perform all tasks in the living cell, are switched on and off in living cells by a mechanism called allosteric control; proteins are regulated by other molecules that bind to their surface, inducing a change of conformation, or distortion in the shape, of the protein, making the protein either active or inactive, Zocchi explained.

Cyclic AMP (cAMP) binds to PKA’s regulatory subunit and induces a change of conformation which leads to the catalytic subunit’s detaching from the regulatory subunit; this separation of the two subunits is how the enzyme complex is turned on in the cell, Zocchi said.

“We can activate the enzyme mechanically, while leaving intact the natural activation mechanism by cAMP” said Zocchi, a member of the California NanoSystems Institute. “We believe this approach to protein control can be applied to virtually any protein or protein complex.

Zocchi’s group first demonstrated mechanical control of protein conformation last year, when the physicists attached a controllable molecular spring, made of a short piece of DNA, to a protein and used it to inhibit its function. In the new research, the group succeeded in activating the enzyme PKA through the same principle, by using the molecular spring to induce the change in conformation which, in the cell, is induced by the natural activator of PKA (the signaling molecule cAMP).

Zocchi’s group can mimic with mechanical tension the natural allosteric mechanism by which PKA is regulated by cAMP. PKA is significantly more complex than the protein that Zocchi’s group used last year.

What are Zocchi’s future research plans?

“I want to see whether we can make molecules which kill a cell based on the genetic signature of the cell,” Zocchi said. “Cancer cells would be an obvious application. This will however require many further steps. So far, we have only worked in vitro. The exciting part is, from the outside, cancer cells can look like normal cells, but inside they carry a genetic mark.

“In the future, perhaps we can control more complicated molecular machines such as ribosomes,” he said. Many antibiotics work by blocking the ribosome of bacteria.

California’s largest university, UCLA enrolls approximately 38,000 students per year and offers degrees from the UCLA College of Letters and Science and 11 professional schools in dozens of varied disciplines. UCLA consistently ranks among the top five universities and colleges nationally in total research-and-development spending, receiving more than $820 million a year in competitively awarded federal and state grants and contracts. For every $1 state taxpayers invest in UCLA, the university generates almost $9 in economic activity, resulting in an annual $6 billion economic impact on the Greater Los Angeles region. The university’s health care network treats 450,000 patients per year. UCLA employs more than 27,000 faculty and staff, has more than 350,000 living alumni and has been home to five Nobel Prize recipients.

####

Contact:
Stuart Wolpert
UCLA
swolpert@support.ucla.edu
(310) 206-0511

Copyright © UCLA

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

Possible Futures

Advances in priming B cell immunity against HIV pave the way to future HIV vaccines, shows quartet of new studies May 17th, 2024

International research team uses wavefunction matching to solve quantum many-body problems: New approach makes calculations with realistic interactions possible May 17th, 2024

Aston University researcher receives £1 million grant to revolutionize miniature optical devices May 17th, 2024

Gene therapy relieves back pain, repairs damaged disc in mice: Study suggests nanocarriers loaded with DNA could replace opioids May 17th, 2024

Molecular Machines

First electric nanomotor made from DNA material: Synthetic rotary motors at the nanoscale perform mechanical work July 22nd, 2022

Nanotech scientists create world's smallest origami bird March 17th, 2021

Controlling the speed of enzyme motors brings biomedical applications of nanorobots closer: Recent advances in this field have made micro- and nanomotors promising devices for solving many biomedical problems October 13th, 2020

Giant nanomachine aids the immune system: Theoretical chemistry August 28th, 2020

Nanomedicine

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Advances in priming B cell immunity against HIV pave the way to future HIV vaccines, shows quartet of new studies May 17th, 2024

New micromaterial releases nanoparticles that selectively destroy cancer cells April 5th, 2024

Announcements

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Finding quantum order in chaos May 17th, 2024

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in cuprate superconductor May 17th, 2024

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project