Amphipathic helix insertions

The emission of Trp 19 in melittin shifts to the red side peaking at 341 nm (Fig. 18), and the probe location slightly moves away from the lipid interface toward the channel center. Consistently, we observed a larger fraction of the ultrafast solvation component (35%) and a smaller contribution of slow ordered-water motion (38%). Melittin consists of 26 amino acid residues (Fig. 9), and the first 20 residues are predominantly hydrophobic, whereas the other 6 near the carboxyl terminus are hydrophilic under physiological conditions. This amphipathic property makes melittin easily bound to membranes, and extensive studies from both experiments [156-161] and MD simulations [162-166] have shown the formation of an 7-helix at the lipid interface. Self-assembly of 7-helical melittin monomers is believed to be important in its lytic activity of membranes [167-169]. Our observed hydration dynamics are consistent with previous studies, which support the view that melittin forms an 7-helix and inserts into the lipid bilayers and leaves the hydrophilic C-terminus protruding into the water channel. The orientational relaxation shows a completely restricted motion of Trp 19, and the anisotropy is constant in 1.5 ns (Fig. 20b), which is consistent with Trp 19 located close to the interface around the headgroups and rigid well-ordered water molecules. 

Hollow structures can also be prepared by the self-assembly of stave or rod-like subunits into barrel or bundle-shaped frameworks. This is one of the most common strategies in nature for channel formation, where the rod-like molecules of the barrel-stave type are /S-sheets or a-helices of amphipathic character. The central cavity has hydrophilic properties, while the lipophilic area is oriented outward, in contact with the membrane of the cell. A natural example of this type of protein is a-hemolysin, a bacterium toxin formed by seven identical subunits that self-assemble when in contact with the cell membrane. This assembly gives rise to a mushroom-shaped structure, whose trunk is formed by a -barrel that is inserted into the cell membrane. The resulting channel has a diameter of 13 A at its narrowest point and can transport ions and other molecules. Other natural examples based on this model —but using an a-helix instead of f-sheets—include cholera toxin, potassium channels, porins, aquaporins, and the most powerful toxin known to date, botulinum neurotoxin (BoNT, known as Botox), broadly studied by Mental s group. ... 

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