Figure 7.

The “linear lattice” versus “emergent conformation” hypotheses for expanded polyQ conformation. The linear lattice model posits that a relatively unstructured epitope of polyQ in wt-htt repeats itself as the polyQ stretch expands. The emergent conformation model posits that expansion of the polyQ stretch induces a conformational change, such that wild-type and mutant polyQ are in distinct conformations. As shown in the middle panel, the linear lattice and emergent conformation hypotheses are not mutually exclusive; both models may be simultaneously true for mHtt. Alternatively, some mHtt molecules may exhibit linear lattice epitope repeats, while others may display an emergent conformation, possibly in the same neuron. Assessment of prognostic value for both epitopes by Cox analysis reveals that the emergent conformation, recognized by 3B5H10, is more toxic or more closely related to a toxic species than the linear lattice epitope, recognized by MW1.