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Publication Abstract from PubMed

The alpha-helix is pre-eminent in structural biology(1) and widely exploited in protein folding(2), design(3) and engineering(4). Although other helical peptide conformations do exist near to the alpha-helical region of conformational space-namely, 310-helices and pi-helices(5)-these occur much less frequently in protein structures. Less favourable internal energies and reduced tendencies to pack into higher-order structures mean that 310-helices rarely exceed six residues in length in natural proteins, and that they tend not to form normal supersecondary, tertiary or quaternary interactions. Here we show that despite their absence in nature, synthetic peptide assemblies can be built from 310-helices. We report the rational design, solution-phase characterization and an X-ray crystal structure for water-soluble bundles of 310-helices with consolidated hydrophobic cores. The design uses six-residue repeats informed by analysing 310-helical conformations in known protein structures, and incorporates alpha-aminoisobutyric acid residues. Design iterations reveal a tipping point between alpha-helical and 310-helical folding, and identify features required for stabilizing assemblies of 310-helices. This work provides principles and rules to open opportunities for designing into this hitherto unexplored region of protein-structure space.

De novo design of discrete, stable 310-helix peptide assemblies.,Kumar P, Paterson NG, Clayden J, Woolfson DN Nature. 2022 Jun 22. pii: 10.1038/s41586-022-04868-x. doi:, 10.1038/s41586-022-04868-x. PMID:35732733^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.