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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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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| author | Rubén López-Sánchez Miguel Mompeán Douglas V. Laurents |
| author_facet | Rubén López-Sánchez Miguel Mompeán Douglas V. Laurents |
| author_sort | Rubén López-Sánchez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d203f0c9645e457296556831a0fa7cbf |
| institution | DOAJ |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-d203f0c9645e457296556831a0fa7cbf2025-08-20T03:03:27ZengNature PortfolioCommunications Chemistry2399-36692025-07-018111610.1038/s42004-025-01576-1Orientation affects hydrogen bonding cooperativity in polyproline II helical bundlesRubén López-Sánchez0Miguel Mompeán1Douglas V. Laurents2Instituto de Química Física “Blas Cabrera” - CSICInstituto de Química Física “Blas Cabrera” - CSICInstituto de Química Física “Blas Cabrera” - CSICAbstract 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.https://doi.org/10.1038/s42004-025-01576-1 |
| spellingShingle | Rubén López-Sánchez Miguel Mompeán Douglas V. Laurents Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles Communications Chemistry |
| title | Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles |
| title_full | Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles |
| title_fullStr | Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles |
| title_full_unstemmed | Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles |
| title_short | Orientation affects hydrogen bonding cooperativity in polyproline II helical bundles |
| title_sort | orientation affects hydrogen bonding cooperativity in polyproline ii helical bundles |
| url | https://doi.org/10.1038/s42004-025-01576-1 |
| work_keys_str_mv | AT rubenlopezsanchez orientationaffectshydrogenbondingcooperativityinpolyprolineiihelicalbundles AT miguelmompean orientationaffectshydrogenbondingcooperativityinpolyprolineiihelicalbundles AT douglasvlaurents orientationaffectshydrogenbondingcooperativityinpolyprolineiihelicalbundles |