As you pick up this issue of the Nexus and turn the page to the Science & Tech section, millions of membrane proteins are hard at work inside your body. All the body’s functions, from movement to cell-to-cell communication, are aided by some kind of membrane protein.
And yet, despite the breadth of control these proteins maintain, the science community has struggled to decipher the structure of these intricate and important molecules.
That is, until UCSB’s Han Research Group, a physical chemistry laboratory headed by Professor Song-I Han, recently developed a tool that is able to study the complexes of these membrane proteins.
The tool involves using the water gradient in the lipid membranes of cells to uncover protein structure. Once the group, led by postdoctoral scholar Chi-Yuan Cheng, developed their technique, they tested their idea in collaboration with Ralf Langen, an associate professor of biochemistry and molecular biology in the University of Southern California’s Keck School of Medicine.
The Han Research Group’s work with Langen’s proteins proved successful in uncovering the elusive membrane protein form. Their technique involved attaching a spin label to a protein and transferring the polarization produced by the excited label to a water molecule, where it revealed the structure of the surrounding water.
“We implant a so-called spin label into the protein, which has a very strong, local magnetic field. We excite this spin label and upon excitation you can transfer the very high polarization from the spin label to the hydrogen of the water, so we get a very high signal enhancement,” Han said. “This signal enhancement can be translated into water dynamics.”
The group then measured the signal enhancement, which can be translated into a water gradient. The water gradient across the lipid bilayer is heterogeneous, and thus gives a molecular ruler for studying the structure of the protein.
Membrane proteins are often drug therapy targets because they help regulate many cell functions, and so understanding their form is crucial. Until now, a lack of instruments capable of performing measurements on protein complexes prevented a comprehensive understanding of their structure. Han’s innovative new technique, however, may aid in developing improved drug targeting and delivery. She said that the next step is to examine the structures of lesser-known proteins.
“The goal is to then use membrane proteins, whose structure and ability to interact with the membrane are not known, to study real problems. So far this was presented on model proteins whose structures are partly known,” said Han. “Now that we have demonstrated it is possible, we can go ahead to solve more realistic interactions of unknown species.”
A version of this article appeared on page 5 of Tuesday October 8, 2013′s print edition of The Daily Nexus.