Role of β-turn residues in β-hairpin formation and stability in designed peptides 1 1Edited by A.R. Fersht
Abstract
The sequence RGITVNGKTYGR has been reported as part of a de novo design peptide system. This peptide folds as a beta-hairpin structure with three residues per strand and two residue turns. Asn6 side-chain, the residue in position L1 of the beta-turn, appeared to be solvent exposed, interacting only within the turn but not with the rest of the peptide. We have chosen this position as a good candidate to design mutations, based on the protein database statistical abundances, that should mainly affect the turn stability and possibly the pairing between strands. We have found that all NMR parameters, in particular the conformational shift analysis of CalphaH and the coupling constants, 3JHNalpha, correlate very well and show similar conformational features in all the turn mutant peptides. The population estimates are in reasonable agreement among the different methods used. It appears that the peptide with Asn in position L1 is the most structured peptide, followed by the one with Asp6. The next structured peptide is the one with Gly6. The least populated peptides were those with Ala6 and Ser6. We have found a strong correlation between the hairpin population, as determined from the conformational shift of CalphaH and the occurrence of the different residues at position L1 of beta-hairpins with type I' beta-turn, in the protein database. Our analysis demonstrates that this peptide system is sensitive enough to register small energy changes in the hairpin structure; therefore, it constitutes an appropriate model to quantify energy contributions, once the appropriate sheet/coil transition algorithm is developed. Comparison with the other studies indicate that the design of a specific hairpin structure must involve a sequence at the turn region favouring the desired turn type, and a sequence at the strands that avoids alternative interstrand side-chain pairings.
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α-helix and β-sheet structures are the most stable secondary structures in proteins, mainly due to their high hydrogen bond content; β-turns and random coils are considered less stable due to their lack of hydrogen bonds and other stabilizing interactions.
“Previous studies have shown that α-helix and β-sheet structures are the most stable secondary structures in proteins, mainly due to their high hydrogen bond content (Wang et al., 2014).In contrast, β-turns and random coils are considered less stable due to their lack of hydrogen bonds and other stabilizing interactions (Ramírez-Alvarado et al., 1997).”
From Impact of lactic acid bacteria coculture on the quality characteristics of goat cheese during ripening (2025) · cites this paper as Ramírez-Alvarado et al., 1997
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- Authors
- Ramı́rez-Alvarado, M., Blanco, F. J., Niemann, H., & Serrano, L.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Ramı́rez-Alvarado, Marina
- Blanco, Francisco J
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 273
- Issue
- 4
- Pages
- 898-912
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2090208503
- Cited by
- 136
- References
- 61
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 6 · 2012: 3
- Type
- book review
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universidad Nacional Autónoma de México
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- beta-turn, beta-hairpin, de novo peptide design, aspartic acid, glycine, alanine, serine, population analysis
- MeSH terms
- Amino Acid Sequence, Circular Dichroism, Models, Molecular, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Solutions, Drug Design, Protein Engineering, Databases, Factual, Protein Structure, Secondary, Protein Folding
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