Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles
Abstract Hydrogen bond cooperativity (HBC) is the phenomenon where the collective strengthening of hydrogen bonds, by mutual polarization and non-additive electrostatic effects, in a network exceeds the sum of individual interactions. HBC has been well-studied in α-helices and β-sheets, where it cri...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01576-1 |
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| Summary: | Abstract Hydrogen bond cooperativity (HBC) is the phenomenon where the collective strengthening of hydrogen bonds, by mutual polarization and non-additive electrostatic effects, in a network exceeds the sum of individual interactions. HBC has been well-studied in α-helices and β-sheets, where it critically stabilizes amyloid structures. During the last 20 years, several natural proteins were characterized which contain multiple aligned and hydrogen-bonded polyproline II (PPII) helices. HBC was recently reported for these PPII helices when arranged along one parallel layer, but its existence in the more abundant antiparallel or mixed parallel/antiparallel PPII assemblies is still unknown. Utilizing computational approaches validated through experimental observables, we report that both canonical CO···HN and non-canonical CO···HαCα hydrogen bonds exhibit mutual reinforcement, revealing a complex hydrogen bonding scheme that manifests HBC in antiparallel PPII helices and in mixed parallel/antiparallel orientations. These findings have fundamental relevance for understanding protein conformational stability and implications for PPII helices as a structural building block for protein design. |
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| ISSN: | 2399-3669 |