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Fig. 51: Assembly pathways of tubulin in the presence of spermine. a-c) Time-resolved synchrotron SAXS and time-resolved cryo-EM results. A cold (9°C) solution of 4 mg/ml tubulin reacted with (a) 1 mM, (b) 5 mM, or (c) 20 mM spermine. The insets compare synchrotron SAXS data at @ 48 h with the last kinetic measurement that showed structural changes. Scale bars are in nm. d) Transformation of bundles of conical spiral structures (purple) into inverted tubules (green) after the spermine concentration was increased to 30 mM and the temperature was increased to 25°C. The inset shows the mass fractions of conical spiral structures and inverted tubules as a function of time. e) Schematic illustration of tubulin assemblies as a function of incubation time and spermine concentration. Cartoons are not to scale.
Natural polyamines are cellular polycations, present at fluctuating concentrations, reaching about 1 mM at certain cell cycle stages, and interacting with anionic cytoskeletal filaments such as actin and microtubule. Polyamines are essential for cell proliferation and growth. Increased uptake of natural polyamines may have
protective effects against cancer, metabolic disease, heart disease and neurodegeneration . The tetravalent cation spermine was found to be effective in promoting tubulin assembly and bundle formation, most likely by forming ion-bridges between adjacent tubulin subunits [1,3].