How Do Glycine-Induced Bent Structures Influence Hierarchical Nanostructuring and Suprastructural Handedness in Short...

Despite the multiple roles of flexible and achiral Gly in regulating protein architectures and functions, its high flexibility is seldom exploited as a structural modulator in the design of self-assembling peptides. By using minimalistic peptide sequences, the effects of Gly insertions are investigated on the molecular conformation and the supramolecular morphology, focusing on Gly-induced bent structures and their impact on self-assembled nanostructures and handedness. Different backbone bending degrees are generated by varying Gly position, which in turn resulted in distinct hydrogen bonding modes and residue shifting upon dimerization, eventually leading to β-sheets and nanofibrils with opposite handedness. The bent structures are revealed to be primarily caused by van der Waals interactions between either the side chains themselves or the side chain and the local backbone around the inserted Gly, in sharp contrast to canonical β-turns stabilized by intrastrand hydrogen bonding. Hence, changing the side chain orientations of adjacent residues by chiral substitution can destabilize the bent structures, leading to wide ribbons with suprastructural chiral racemization. This study not only helps understand the versatile roles of Gly in protein architectures but also serves as a paradigm for tuning peptide supramolecular nanostructures and handedness via Gly insertion.