Friday, September 08, 2006

Protein Folding News

A news release entitled 'Cornell and Scripps researchers propose theory of how proteins fold into their critical shapes' details some recent findings related to the mystery of protein folding. Part of the story follows in italics interspersed with my comments in standard form.


Experimental evidence provided by a Cornell researcher and colleagues at the Scripps Research Institute in La Jolla, Calif., supports a long-held theory of how and where proteins fold to create their characteristic shapes and biological functions.

The theory proposes that proteins start to fold in specific places along an amino acid chain (called a polypeptide chain) that contains nonpolar groups, or groups of molecules without a charge, and continue to fold by aggregation, i.e., as several individuals of these nonpolar groupings combine. Using the same principle that separates oil and water, these molecules are hydrophobic -- they avoid water and associate with each other.

In the water-based cell fluid, where long polypeptide chains are manufactured and released by ribosomes, the polypeptide chains rapidly fold up into their biologically functional structure. The theory proposes that there are sites along the polypeptide chains where hydrophobic groups initially fold in on themselves, creating small nonpolar (hydrophobic) pockets that are protected from the water.


These pockets tend to be found in the core of proteins. Cellular membrane proteins are ready examples.

The first method used supercomputers to calculate the energy required to convert a polypeptide chain into a collapsed hydrophobic pocket. The folds occur in several places that require the least possible energy to maintain. By finding these places where the nonpolar groups exist, the researchers better understand where folding occurs along a linear polypeptide chain.

Search criteria includes both the minimal energy and non-polar amino acid side chain factors.

The second method involved mapping a folded protein by tracing the folding steps required to arrive at the protein's native structure. This method mapped three stages of folding. First, the short-range contacts between amino acids that are very close to each other were mapped, revealing the initial nonpolar (hydrophobic) folds. The next two stages show folds that occur between points that are farther from each other along the polypeptide chain. These secondary folds may attach two or three hydrophobic pockets.

These two methods were used together in this study to pinpoint where on a polypeptide chain the nonpolar segments occur and where initial folding takes place and then propagates to the final folded form.


Each protein contains a massive amount of information. Yet this problem appears to be slowly yielding to research efforts. A recent post discussed the chaperone role played by some proteins in the folding of others. Since misfolding leads to malfunction and disease the importance of the topic is evident.

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