Direct detection of an NH-π hydrogen bond in an intrinsically disordered peptide

Hydrogen bonds play crucial roles in functional biomolecular dynamics. It is suggested that non-conventional hydrogen bonds engaging π electrons are prevalent in proteins. The experimental support for their existence is however limited. Here, we provide direct NMR spectroscopic evidence for the existence of an NH-π interaction in an intrinsically disordered peptide (E22G-Aβ40). In particular, we demonstrate the correlation between the amide proton of a glycine residue (Gly22) and the aromatic carbons of its preceding Phe20 through π hydrogen bond-mediated scalar coupling between them, as predicted by density functional theory calculations. Our results present a proof-of-principle example of NH-π interactions in an intrinsically disordered protein (IDP) and suggest the potential prevalence of π hydrogen bonds on the surface of IDPs. Direct experimental verification of NH-π interactions in folded proteins remains for future studies.

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Publication Details

Journal
Nature Communications
Published
2025-11-20
DOI
https://doi.org/10.1038/s41467-025-66013-2
Citations
1
Primary Topic
Crystallography and molecular interactions
Type
article
Field-Weighted Citation Impact
1.75

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article

Direct detection of an NH-π hydrogen bond in an intrinsically disordered peptide

Karin Giller, Mehdi D. Davari, Robin Backer, Kerstin Overkamp et al.
1 citations
Nature Communications
Crystallography and molecular interactions
1.75
article

Direct detection of an NH-π hydrogen bond in an intrinsically disordered peptide

Karin Giller, Mehdi D. Davari, Robin Backer, Kerstin Overkamp, Nasrollah Rezaei‐Ghaleh, Fatima Matroodi, Christian Griesinger, Stefan Becker, D. N. DHAR, Barbara Rossi, Dieter Willbold, L. Russo
article en
1 citations

Abstract

Hydrogen bonds play crucial roles in functional biomolecular dynamics. It is suggested that non-conventional hydrogen bonds engaging π electrons are prevalent in proteins. The experimental support for their existence is however limited. Here, we provide direct NMR spectroscopic evidence for the existence of an NH-π interaction in an intrinsically disordered peptide (E22G-Aβ40). In particular, we demonstrate the correlation between the amide proton of a glycine residue (Gly22) and the aromatic carbons of its preceding Phe20 through π hydrogen bond-mediated scalar coupling between them, as predicted by density functional theory calculations. Our results present a proof-of-principle example of NH-π interactions in an intrinsically disordered protein (IDP) and suggest the potential prevalence of π hydrogen bonds on the surface of IDPs. Direct experimental verification of NH-π interactions in folded proteins remains for future studies.

Nature CommunicationsVol. 16(1)
Forschungszentrum Jülich (DE), University of Trento (IT), University of Ferrara (IT), University of Pavia (IT), Elettra-Sincrotrone Trieste S.C.p.A. (IT), Leibniz Institute of Plant Biochemistry (DE), John von Neumann Institute for Computing (DE), University of Campania "Luigi Vanvitelli" (IT), Max Planck Institute for Multidisciplinary Sciences (DE), Heinrich Heine University Düsseldorf (DE)
Elettra-Sincrotrone Trieste, Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 11%
Crystallography and molecular interactions
1.75
DOIOpen Access PDFOpenAlex
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