POKEY FOLDING RATES DEFY PREDICTIONS
STU BORMAN · Chemical & Engineering News · 2003
A LARGE PROTEIN KNOWN AS VlsE has been found to fold via a mechanism generally used only by small proteins and to fold four orders of magnitude more slowly than the rate predicted by relative contact order—a property of protein architecture widely used to forecast folding rates. A second, still preliminary study has obtained similar results with another protein. The surprising findings could make it necessary to reevaluate current thinking on the relationship of protein structure to folding mechanism and rate. The VlsE study was carried out by grad student KathrynJones and associate professor of chemistry Pernilla Wittung- Stafshede of Tulane University, New Orleans { J.f.Am. Chem. Soc., 125, 9606 (2003)]. They show that this very large protein, with 341 residues, folds by a two-state kinetic mechanism, which has previously been observed only in proteins less than half that size. In a two-state kinetic mechanism, an unfolded protein chain folds into its native form without any ...