Penn researchers find proteins more dynamic than previously known

May 22, 2001

Proteins are far more active and dynamic than scientists have imagined, say researchers at the University of Pennsylvania School of Medicine. Their study, to be published Thursday in the journal Nature, affords the first comprehensive view scientists have had of a protein's internal motion. "The interior of a protein is much more liquid-like than scientists originally anticipated. Everything is moving, and it's moving all the time, very fast," said A. Joshua Wand, PhD, Professor of Biochemistry and Biophysics at Penn and principal author of the study.

"The really exciting thing is they move so much that, potentially, it dramatically influences how they work," Wand said. "This is the beginning of a long new story that, fundamentally, will have a lot to do with understanding protein function."

Wand and his colleague used nuclear magnetic resonance (NMR) relaxation imaging to track the activity of the calmodulin-peptide protein complex across a spectrum of 13 temperature settings that ranged from 278 degrees Kelvin to 346 degrees Kelvin (from 15 degrees Celsius to 73 degrees Celsius). The NMR data demonstrate that a much larger range of internal motion is present in calmodulin than crystallographic studies -- the standard method of discerning protein properties -- have had the capacity to demonstrate.

"The beauty of this experimental study is that motion and temperature are inextricably linked, and by understanding how motion changes in response to temperature, you understand more about the motions themselves," said Andrew Lee, PhD, a researcher who worked on the study with Wand at Penn as a postdoctoral fellow before taking a faculty position at the University of North Carolina. He added: "The common thinking has been that the structure of proteins dictates their functions, and that each one has a different biochemical task. But they aren't static structures -- they fluctuate, and that these fluctuations are also critical for protein activity."

In their research, Wand and Lee found the calmodulin protein has three distinct bands (or preferred magnitudes) of motion on a subnanosecond time scale, a richness of variation that was not previously known. Further, when they compared those findings with existing data on other proteins that had been studied at single temperatures, Wand and Lee discovered the same spectrum of motion. This suggests that the range of motion is a general fundamental property of proteins.

According to Wand, the research findings also suggests an explanation for the "glass transition" characteristic of proteins -- the feature that makes proteins respond to heat in the same fashion as glass. (The onset of dynamics in the glass transition is often associated with the attainment of biological activity.)

"The key word is 'entropy' -- the ability to assume multiple states," Wand said. "For a long time, people assumed proteins didn't have significant entropy, so they discounted its potential functional role. In fact, proteins have a lot more ways to accomplish their functions than we realized. This dynamism has central significance for how proteins may work."

"People tend to think of proteins as static, because they see pictures of them as snapshots. But now scientists will have to start considering the effects of entropy and dynamics," Lee added.

The new, more dynamic picture of proteins also offers a new direction for pharmaceutical companies that may eventually enable them to enhance the effectiveness of drugs by targeting more accessible protein sites, Wand said.
The research was funded by the National Institutes of Health.

Editor's note: Dr. Wand may be reached directly at: 215-573-7288

University of Pennsylvania School of Medicine

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to