Cited by 28Calcium Carbonate Crystallization and InhibitionProtein Structure and DynamicsDiatoms and Algae Research

Equilibrium Conformational Ensemble of the Intrinsically Disordered Peptide n16N: Linking Subdomain Structures and Function in Nacre

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Brown, Aaron H., Rodger, P. Mark, Evans, John Spencer, Walsh, Tiffany R.·2014·Biomacromolecules

Abstract

n16 is a framework protein family associated with biogenic mineral stabilization, thought to operate at three key interfaces in nacre: protein/β-chitin, protein/protein, and protein/CaCO3. The N-terminal half of this protein, n16N, is known to be active in conferring this mineral stabilization and organization. While some details relating to the stabilization and organization of the mineral are known, the molecular mechanisms that underpin these processes are not yet established. To provide these molecular-scale details, here we explore current hypotheses regarding the possible subdomain organization of n16N, as related to these three interfaces in nacre, by combining outcomes of Replica Exchange with Solute Tempering molecular dynamics simulations with NMR experiments, to investigate the conformational ensemble of n16N in solution. We verify that n16N lacks a well-defined secondary structure, both with and without the presence of Ca(2+) ions, as identified from previous experiments. Our data support the presence of three different, functional subdomains within n16N. Our results reveal that tyrosine, chiefly located in the center of the peptide, plays a multifunctional role in stabilizing conformations of n16N, for intrapeptide and possibly interpeptide interactions. Complementary NMR spectroscopy data confirm the participation of tyrosine in this stabilization. The C-terminal half of n16N, lacking in tyrosine and highly charged, shows substantive conformational diversity and is proposed as a likely site for nucleation of calcium carbonate. Finally, dominant structures from our predicted conformational ensemble suggest the presentation of key residues thought to be critical to the selective binding to β-chitin surfaces.

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Crossref · 10.1021/bm501263s

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  • The conformational ensemble of n16N, an intrinsically disordered peptide, has dominant structures that place key residues in locations thought critical for selective binding to β-chitin surfaces, as shown by REMD combined with NMR.

    “However, a combination of replica exchange molecular dynamics simulations with NMR experiments showed that in the equilibrium conformational ensemble of the intrinsically disordered peptide the dominant structures present the key residues in locations thought to be critical for selective binding to β-chitin surfaces.258”

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Authors
Brown, A. H., Rodger, P. M., Evans, J. S., & Walsh, T. R.
Affiliations
  • Deakin University (AU)
  • University of Warwick (GB)
  • New York University (US)
Corresponding author
Walsh, Tiffany R.
Venue
Biomacromolecules
Published
2014-11-20
Volume
15
Issue
12
Pages
4467-4479
ISSN
  • 1525-7797 (ISSN-L)
  • 1526-4602
OpenAlex
W2012016586
Cited by
28
References
101
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 6 · 2015: 4
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Biomacromolecules (publishedVersion)
  • PubMed (publishedVersion)
  • Deakin Research Online (Deakin University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Engineering and Physical Sciences Research Council (EP/I001514/1)
  • University of Warwick
  • Deakin University
Topics
  • Physical Sciences › Materials Science › Biomaterials › Calcium Carbonate Crystallization and Inhibition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Biomaterials › Diatoms and Algae Research
Keywords
nacre, intrinsically disordered peptides, conformational ensembles, tyrosine, calcium carbonate nucleation, biomineralization, calcium ions
MeSH terms
Binding Sites, Calcium Carbonate, Chitin, Magnetic Resonance Spectroscopy, Peptides, Protein Conformation, Cluster Analysis, Protein Structure, Secondary, Molecular Dynamics Simulation, Nacre, Intrinsically Disordered Proteins

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