Chirality transmission in macromolecular domains

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Chiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates. We find that right-handed DNA triple helices well accommodate peptide triple coiled-coils of the same handedness, but not with the left-handed coiled-coil stereoisomers. This chiral communication is effective in a range (<4.5 nm) far beyond canonical IMF distance. Small-angle X-ray scattering and molecular dynamics simulation indicate that the interdomain linkers are tightly packed via hydrophobic interactions, which likely sustains the chirality transmission between DNA and peptide domains. Our findings establish that long-range chiral transmission occurs in tertiary macromolecular domains, explaining the presence of homochiral pairing of superhelices in proteins.

Original languageEnglish
Article number76
JournalNature Communications
Issue number1
Number of pages11
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The VILLUM FONDEN is thanked for funding the Biomolecular Nanoscale Engineering Center (BioNEC), a VILLUM center of excellence, grant number VKR18333 (C.L., K.J.J. and J.W). H.M. thanks the National Institutes of Health [NIH 1R01CA236350] for biophysical evaluations; and National Science Foundation [CBET-1904921] for DNA construct preparations and instrument maintenance and usage. Joan Hansen and Tina Grubbe Hansen are thanked for technical assistance on oligonucleotide synthesis and purification. Kasper K. Sørensen is thanked for technical assistance on peptide synthesis and purification. Josephine Tuborg Boesen and Peter W. Thulstrup are thanked for the assistance on the CD measurement.

Publisher Copyright:
© 2022, The Author(s).

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