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

New electrical energy storage material shows its power

August 24, 2016

A powerful new material developed by Northwestern University chemist William Dichtel and his research team could one day speed up the charging process of electric cars and help increase their driving range.

Calcium channel blockers caught in the act at atomic level

August 24, 2016

An atomic level analysis has revealed how two classes of calcium channel blockers, widely prescribed for heart disease patients, produce separate therapeutic effects through their actions at different sites on the calcium ...

Bio-inspired tire design: Where the rubber meets the road

August 24, 2016

The fascination with the ability of geckos to scamper up smooth walls and hang upside down from improbable surfaces has entranced scientists at least as far back as Aristotle, who noted the reptile's remarkable feats in his ...

Selecting the right house plant could improve indoor air

August 24, 2016

Indoor air pollution is an important environmental threat to human health, leading to symptoms of "sick building syndrome." But researchers report that surrounding oneself with certain house plants could combat the potentially ...

0 comments

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.