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Cited by 139Protein Structure and DynamicsElectron Spin Resonance StudiesIon channel regulation and function

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

The Role of Proline and Glycine in Determining the Backbone Flexibility of a Channel-Forming Peptide

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Jacob, Jaison, Duclohier, Herve, Cafiso, David S.·1999·Biophysical Journal
DOI 10.1016/s0006-3495(99)77298-xPMC PMC1300115
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Abstract

Alamethicin is a helical 20-amino acid voltage-gated channel-forming peptide, which is known to exhibit segmental flexibility in solution along its backbone near alpha-methylalanine (MeA)-10 and Gly-11. In an alpha-helical configuration, MeA at position 10 would normally hydrogen-bond with position 14, but the presence of proline at this position prevents the formation of this interhelical hydrogen bond. To determine whether the presence of proline at position 14 contributes to the flexibility of this helix, two analogs of alamethicin were synthesized, one with proline 14 replaced by alanine and another with both proline 14 and glycine 11 replaced by alanine. The C-termini of these peptides were derivatized with a proxyl nitroxide, and paramagnetic enhancements produced by the nitroxide on the Calpha protons were used to estimate r-6 weighted distances between the nitroxide and the backbone protons. When compared to native alamethicin, the analog lacking proline 14 exhibited similar C-terminal to Calpha proton distances, indicating that substitution of proline alone does not alter the flexibility of this helix; however, the subsequent removal of glycine 11 resulted in a significant increase in the averaged distances between the C- and N-termini. Thus, the G-X-X-P motif found in alamethicin appears to be largely responsible for mediating high-amplitude bending motions that have been observed in the central helical domain of alamethicin in methanol. To determine whether these substitutions alter the channel behavior of alamethicin, the macroscopic and single-channel currents produced by these analogs were compared. Although the substitution of the G-X-X-P motif produces channels with altered characteristics, this motif is not essential to achieve voltage-dependent gating or alamethicin-like behavior.

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Cited by

  • Data-driven de novo design of super-adhesive hydrogels

    Liao, H., Hu, S., Yang, H., Wang, L., Tanaka, S., Takigawa, I., Li, W., Fan, H., & Gong, J. P. (2025) · Nature · doi:10.1038/s41586-025-09269-4 · Cited by 169

    “For consistency in the encoding, glycine, alanine and proline were excluded from the hydrophobic class because of their smaller side chains, which are proposed to have a less important role in interfacial contacts and interactions compared with other amino acids 26 .”

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Metadata

Authors
Jacob, J., Duclohier, H., & Cafiso, D. S.
Affiliations
University of Virginia (US)
Corresponding author
Cafiso, David S.
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
1999-03
Volume
76
Issue
3
Pages
1367-1376
ISSN
0006-3495 (ISSN-L)
DOI
10.1016/s0006-3495(99)77298-x
PMC
PMC1300115
OpenAlex
W2047620716
Cited by
139
References
47
Citations by year
2026: 5 · 2025: 12 · 2024: 4 · 2023: 4 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 8 · 2018: 9 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 1 · 2012: 1
FWCI
1.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM35215, R01GM035215)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Spectroscopy › Electron Spin Resonance Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
alamethicin, proline, glycine, backbone flexibility, alpha-helix, segmental flexibility, voltage-gated ion channels, single-channel currents, peptide analogues
MeSH terms
Alamethicin, Amino Acid Sequence, Binding Sites, Biophysics, Electron Spin Resonance Spectroscopy, Glycine, Hydrogen Bonding, Ion Channels, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Proline, Spin Labels, Protein Structure, Secondary, Amino Acid Substitution, Biophysical Phenomena

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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