Quantifying protein-folding mechanisms

October 15, 2012
Quantifying protein folding mechanisms
Credit: Thinkstock

European scientists are investigating the mechanisms by which proteins fold to form complex configurations using single-molecule experimental techniques.

Proteins are complex three-dimensional (3D) structures formed by chains of (their primary structure). The chains fold and line up to form sheets or helices (secondary structure) and in more complicated ways to form innumerable geometrical configurations directly related to their eventual functions (tertiary and quaternary structures).

The method by which a protein arrives at its final configuration is thought to be governed by its so-called free-energy landscape. Energy landscape theory states that the primary sequence of a protein defines its free-energy landscape which determines its folding pathway and the rates of folding and unfolding.

The path to a protein's final equilibrium state (as well as the properties of the final state itself) is guided by hills and valleys in the energy landscape.

Spectrin is the main component of a that lines the inside surface of (erythrocytes) and is thought to be responsible for maintaining their shape (it is cytoskeletal in nature).

It forms a three-helix bundle where the three different domains (R15, R16 and R17) fold to their native conformations at speeds that vary tremendously, despite their apparently identical structures and properties. Evidence points to diversity in energy landscape 'roughness' as an explanation for the different folding rates – slow-folding domains (R16 and R17) have rough landscapes whereas fast-folding R15 has a smooth one.

Present knowledge of energy landscape roughness comes primarily from theory and computer models. sought to directly investigate the energy landscape of these three spectrin domains.

With funding of the Spectrinroughness project, scientists are employing state-of-the-art single-molecule spectroscopic methods (single-molecule Förster resonance energy transfer, smFRET, and fluorescence correlation spectroscopy, FCS) together with novel mathematical analyses to experimentally quantify energy landscape roughness.

The Spectrinroughness project has already yielded the first measurement on an unfolded native state of certain parameters related to folding. Continued research will no doubt provide novel experimental data and descriptions of roughness as well as tools related to and applications of single-molecule biophysics techniques.

Explore further: Biophysicists manipulate 'zipper,' reveal protein folding dynamics

Related Stories

Protein folding made easy

June 7, 2011

Protein folding has nothing to do with laundry. It is, in fact, one of the central questions in biochemistry. Protein folding is the continual and universal process whereby the long, coiled strings of amino acids that make ...

Invention unravels mystery of protein folding

September 14, 2011

An Oak Ridge National Laboratory invention able to quickly predict three-dimensional structure of protein could have huge implications for drug discovery and human health.

Recommended for you

Scientists create revolutionary material to clean oil spills

November 30, 2015

Deakin University scientists have manufactured a revolutionary material that can clean up oil spills, which could save the earth from potential future disasters such as any repeat of the 2010 Gulf Coast BP disaster that wreaked ...

A new form of real gold, almost as light as air

November 25, 2015

Researchers at ETH Zurich have created a new type of foam made of real gold. It is the lightest form ever produced of the precious metal: a thousand times lighter than its conventional form and yet it is nearly impossible ...


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.