Figure 15. Flattened representations of the proposed α-Syn lipoprotein Type 2P octamer of discs. (a) Two subunits of the inner 24-stranded β-barrel formed by Sy2,4,6. (b) Four subunits of the 32-stranded outer β-barrels formed by Sy1,3,5,8. The Ct domains form 4-stranded antiparallel β sheets that extend in series with the outer β-barrels. The schematic for the Ct barrels on each end of the octamers includes Ct domains from adjacent octamers, enclosed in parallelagrams and in lighter shades. The cylinders in the background represent the β barrels that the strands wrap around. The calculated distance between adjacent discs is ~7.6 nm.
In spite of the absence of the Sy7 segment and substantial sequences differences in Ct1, Ct2, and Ct3, β-Syn discs can be modeled with the same general folding motif as α-Syn (Appendix Fig. A1). The requirement that both families have the same basic structure was used to constrain the end of Sy6 to be proximal to the beginning of Sy8 and that the Sy7 β-hairpin not be an integral component of the α-Syn β-barrels. Ct1 and Ct2 of β-Syn have insertions in the same general spatial region as occupied by Sy7 in the model of α-Syn.
In summary, the structures predicted by these models are consistent with the dimensions of the stacked discs observed in micrographs, and are well designed to bind lipids with zwitterionic head-groups. These non-toxic structures may represent a major functional role for these synucleins in regulating and transporting lipids.