Researchers shed light on how proteins find their shapes

Feb 23, 2009
The UCSD model of the folding energy landscape for cytochrome c. The landscape was probed experimentally at Caltech, using time-resolved fluorescence energy transfer from six donor labels (represented as single spheres of differing colors) to the heme acceptor. [Credit: Peter Weinkam, UCSD]

(PhysOrg.com) -- Researchers from the California Institute of Technology (Caltech) and the University of California at San Diego (UCSD) have brought together UCSD theoretical modeling and Caltech experimental data to show just how amino-acid chains might fold up into unique, three-dimensional functional proteins.

Their insights were recently published in the February 10 issue of the Proceedings of the National Academy of Sciences (PNAS).

The paper details the matching of a series of protein-folding models created by the UCSD team (led by Peter Wolynes, UCSD professor of chemistry and biochemistry and physics) with experimental data gathered using a novel technique created by the Caltech team (led by Faculty Associate in Chemistry Jay Winkler and Harry Gray, Caltech's Arnold O. Beckman Professor of Chemistry and founding director of the Beckman Institute).

The Winkler-Gray method of watching proteins as they crumple and fold involves the use of a picosecond camera that captures fluorescent flashes as a laser pulse excites a donor probe, which emits light and transfers that light to an acceptor probe. The distance between the donor and acceptor change as the amino-acid chain transforms itself into a three-dimensional protein.

In the PNAS paper, the two groups combined the Caltech experimental technique--first described in a 2002 paper published in the Journal of the American Chemical Society--with Wolynes's protein-folding models to see if they could come up with the precise folding pattern of cytochrome c, a protein that is part of the mitochondrial electron-transfer chain that turns food into cellular energy.

At first the models and the experimental data seemed to be describing two entirely different things, according to Winkler. "The researchers had to account for charge-charge interactions between amino acids that appear to be important--the way that like charges repel and opposite charges attract," he explains. "And they had to consider the hydrophobic interactions--the way that oily parts of the proteins like to stick together but are repelled by the watery parts. When their models took account of these interactions, it fit the experimental data."

"It was the first time anyone has been able to develop a theoretical model able to account for the results we've been getting with our time-resolved energy-transfer experiments," adds Gray.

Other coauthors on the PNAS paper, entitled "Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles," are Patrick Weinkam from UCSD and Ekaterina Pletneva, formerly at Caltech and now at Dartmouth College.

Source: California Institute of Technology

Explore further: Digestive brilliance of breast milk unravelled

add to favorites email to friend print save as pdf

Related Stories

Why are women leaving the tech industry in droves?

24 minutes ago

Ana Redmond launched into a technology career for an exciting challenge and a chance to change the world. She was well-equipped to succeed too: An ambitious math and science wiz, she could code faster, with fewer errors, ...

Squeezing out new science from material interfaces

24 minutes ago

With more than five times the thermal conductivity of copper, diamond is the ultimate heat spreader. But the slow rate of heat flow into diamond from other materials limits its use in practice. In particular, ...

Recommended for you

Fluid-filled pores separate materials with precision

4 hours ago

In nature, pores can continuously control how a living organism absorbs or excretes fluids, vapors and solids in response to its environment; for example, tiny holes invisible to the naked eye called stomata ...

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.