Figure 5.

P301 mutations shift the balance from functional to aggregation-prone conformations. Turn conformations (bottom) are required for functional microtubule binding (left), whereas extended conformations (top) are associated with aggregation and the formation of pathogenic fibrils (right). In the wild-type ensemble (P301; bottom), turn-like structures predominate. By contrast, extended structures are significantly populated in the mutant ensemble (P301L; top). The zoom-ins on the right show representative backbone traces around amino acid 301 as tubes.