Fig. 26 shows a hypothetical scheme for how larger Type 1 α-Syn oligomers and channels may develop from Type 1 αβ trimers. In this scheme trimers may merge in solution as illustrated or within the membrane to form hexamers and nonamers, hexamers and nonamers may interact with or within membranes to form transmembrane channels, and nonamers may couple in solution to form octadecamer cylinders. Secondary structure analysis of the cylindrical oligomers [5] indicates the presence of antiparallel β-structure; albeit at a lower percentage than in our model. The dynamic nature of oligomers and the probable simultaneous presence of multiple assemblies and monomers in a prepration of oligomers may complicate evaluation of any specific model based on the results of secondary structure analyses. Figure 26. Hypothesis for development of Type 1 oligomers and channels from merging of Type 1 αβ trimers. Small cylinders represent α-helical hairpins of the Nt domain. Larger blue cylinders represent β-barrels formed by NAC domain β-hairpins. Magenta regions represent disordered or β-barrel Ct domains. (a) Wedge representions of assemblies of six α-Syn monomers viewed from the top. Merging of trimers to form hexamers could occur either in solution as illustrated or within the membrane. The NAC domain is not shown in the last schematic. (b) Assemblies of six α-Syn monomers viewed from the side. The black stripped areas represent membrane alkyl regions. When a soluble trimer or hexamer interacts with a membrane, its Nt domain α-helices may peal away form the NAC domain and interact with lipid headgroups on the membrane’s surface, allowing the NAC β-barrel to penetrate the membrane. The Nt and Ct domains may eventually morph into Type 1P β-barrels. (c) Similar assemblies of nine α-Syn monomers. (d) End-on interactins of two soluble nomamers, each formed from three trimers, to form an assembly with 3-fold radial symmetry and 2-fold perpendicular symmetry. Positions of the Nt α-helices, NAC β-barrels, and Ct domain may then shift to more energetically-favorable positions. Next the 6-stranded NAC barrels may merge to form a 36-stranded β-barrel while the Nt helices rearrange to form concentric 18- and 27-stranded β-barrels and the Ct domains may interact to form a partially surrounding 36-stranded β-barrel. The last rearrangement allows all subunits to have identical conformation and gives the 18-mer 9-fold radial symmetry while maintaining the 2-fold perpendicular symmetry.