Figure 21. Comparison of our model of a nonamer α-Syn channel to the structure of Lysenin. (a & b) Side and top views of ribbon representations of an atomic scale model of the α-Syn channel. The ribbons are colored by a rainbow spectrum beginning with red for the N-termini and ending with magenta for the C-termini. c) Atomic-force microscopy (AFM) image of the extracellular domain of an α-Syn channel (Adapted from Quist et al. [21]. The ovals represent outlines of the Nt (black) and Ct (white) β-barrel walls of the model. (c & d) Side and top views of a cryo-EM-determined structure of Lysenin [31]. e) An AFM image of the extracellular domains of a Lysenin channel (Adepted with permission from Podobnik M, Savory P, Rojko N, et al [66].
Positioning the outer barrel to reduce clashes among side chains while maintaining the radial symmetry permits H-bonding between the strands of each barrel to be maintained while eliminating empty space between the barrels (Figs. 22 d & f). This tight packing is possible because the majority of side-chains between the barrels are small and the pitches of the pleats are similar enough (7.8 and 7.0 nm) for intermeshing-pleats. The distance between the walls of the middle and tentative outer Ct barrel is greater (~ 1.2 nm) and the side-chains are larger and more polar. Excluding the last four resides where the conformation is most ambiguous, all charged side chains inside the Ct barrel (D98, K102, E104, D115, E126, E131, D135) form at least one salt bridge with oppositely charged side-chains of the Nt domain.