Figure 1 - Hypothesized mechanism of httex1 aggregate formation³ (Models 1, 1a and 1b in Supplementary Methods).

Httex1 monomer (httex1) undergoes a conformational change to acquire a misfolded conformation (httex1^*), which may then revert to the original conformation or react with another httex1 molecule to form a dimer. The formation of a httex1 dimer is assumed to be irreversible, rapidly leading to the formation of larger aggregates. (In Model 2, the dimerization step is between two misfolded monomers httex1^*.)