PROTEIN FOLDING

Trapped on the wrong pathway

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Science  17 Jul 2015:
Vol. 349, Issue 6245, pp. 280-281
DOI: 10.1126/science.349.6245.280-d

Protein folding can be described as diffusion over an energy landscape in conformational space to reach an energy minimum that represents a stable folded structure, and it is implicated in many diseases. A particularly dramatic example is the prion protein, PrP, that folds rapidly into a native monomeric structure but also has a stable oligomeric form that causes prion disease. Yu et al. used single-molecule force spectroscopy to monitor misfolding of a PrP dimer. The dimer misfolds along a single pathway involving several intermediates, one of which blocks native folding. Diffusion across the energy landscape is 1000 times slower than for the folding of native prion monomers, probably indicating that many unproductive interactions occur during misfolding.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1419197112 (2015).

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