Unique behaviour of the alpha-helix in bending deformation

The maximum degree of bending that can be tolerated by the rigid rod-like alpha-helix remains unknown; however, it should be very difficult or even impossible to make alpha-helices with varying degrees of curvature in folded proteins. As an experimentally tractable model, here we utilize cyclic proteins and peptides to determine the maximum possible bending in the alpha-helix. We artificially enforced bending in the alpha-helices by using variously sized macrocycles and compared the structural characteristics of the macrocycles with those of their linear counterparts. This differential analysis reveals that the radius of curvature (RC) for the maximally bent alpha-helix is approximately 10 times smaller than those of typical alpha-helices found in natural proteins. Together with the novel finding of the limit of alpha-helix deformation, excessively bent alpha-helices can be further utilized in designing de novo peptides and proteins with unique structures and peculiar functions.