UB Researchers Develop Novel Way To Study Dynamics Of Receptor Proteins

BUFFALO, N.Y. -- Proteins, the workhorses of human cells, exist primarily in two stable states: inactive and active. In order to perform their assigned tasks, they must be triggered to change into the active state.

Structural biologists are learning what protein molecules look like in their stable-state end-points, but very little is known about the instantaneous journey from one state to the other.

Researchers at the University at Buffalo, in the Feb. 17 issue of Nature, report a new way to study the dynamics of proteins as they pass through this transition state.

"To understand how a protein works, it is very important to understand how it moves and changes," said Anthony Auerbach, Ph.D., UB professor of physiology and biophysics, and senior author on the paper. Claudio Grosman, Ph.D., research assistant professor working with Auerbach, is the primary author.

"When we know how the protein moves, perhaps we can make it go faster or slower, or develop drugs to change the ratio of active-to-inactive states," Auerbach said.

The ability to intervene in the transition state eventually could be useful in such conditions as congenital myasthenia syndrome, in which molecules in muscle cells jump too quickly from one state to the other, causing damage to the cell and eventually interfering with movement, he noted.

Grosman and Auerbach have been working with a single protein molecule at the nerve-muscle synapse -- a receptor for the neurotransmitter acetylcholine. Using a standard technique called patch clamp, they have been able to obtain a "snapshot" of several regions of the receptor at the transition state -- the highest energy point between active and inactive states. Their results suggest there is a wave of structural change during receptor activation.

"The resulting map of this conformation wave provides empirical evidence that will serve as guide posts for scientists who will do the computer analysis of the transition state in the future," Auerbach said.

Ming Zhou, Ph.D., a former graduate student in the UB Department of Physiology and Biophysics, now at Rockefeller University, also participated in the research.