Parallel and antiparallel peptide double β-helices controlled by metal-induced folding and assembly

Abstract

Short peptides with sequences of alternating l- and d-residues are known to form antiparallel double β-helical structures, but their equilibrium structures have not been characterized in detail. Here, we use metal coordination of a simple octapeptide, -(l-Val-d-Val)4-, modified with two coordinating side chains at the (i, j)-th residues to uncover these elusive structures. When (i, j) = (3, 5), complexation with ZnI2 induces a parallel double β-helix, which is not commonly seen. In contrast, when (i, j) = (5, 7), a commonly occurring antiparallel double β-helix (Type I) is formed. Interestingly, complexation of the peptide with (i, j) = (3, 7) gives another antiparallel double β-helix, the unknown Type II structure, which has an inverted orientation of the two strands. Complexation of a monotopic peptide (i = 3) with trans-PdCl2 yields a Pd(II)-linked dimeric bundle of two antiparallel β-helices. These results demonstrate that metal coordination can induce even as-yet unrecognized structures in the folding and assembly pathways of short peptides. Key points: Structural elucidation of elusive peptide nanostructures Precise structural control of double helical molecules Fusion of peptide folding and metal-directed self-assembly.