Biochemistry

Downhill from Here?

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Science  17 Dec 2004:
Vol. 306, Issue 5704, pp. 2003
DOI: 10.1126/science.306.5704.2003d

In the classical theory of protein folding, distinct native and denatured states are separated by an energy barrier, and transitions between the two are cooperative. An alternative model has been proposed in which the denatured state gradually merges into the native state as conditions change, with no significant energy barrier. Such downhill protein folding has been suggested for a fluorescently labeled version of the all-helical bacterial protein BBL (Garcia-Mira et al., Reports, 13 Dec. 2002, p. 2191). Now Ferguson et al. suggest that the results may have been influenced by the labelling of BBL. Thermal denaturation of unlabeled wild-type BBL and two homologs was highly cooperative, with similar transition midpoints being obtained by a variety of techniques. In contrast, the introduction of extrinsic fluorophores into BBL complicated its unfolding behavior. Thus, downhill folding may occur for some proteins that do not have distinct folded states but is unlikely to be used by well-folded proteins such as BBL. — VV

J. Mol. Biol. 344, 295 (2004).

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