Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre

Brown,AH, Rodger,PM, Evans,JS and Walsh,TR 2014, Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre, Biomacromolecules, vol. 15, no. 12, pp. 4467-4479, doi: 10.1021/bm501263s.

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Title Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre
Author(s) Brown,AH
Walsh,TRORCID iD for Walsh,TR orcid.org/0000-0002-0233-9484
Journal name Biomacromolecules
Volume number 15
Issue number 12
Start page 4467
End page 4479
Total pages 13
Publisher American Chemical Society
Place of publication Washington DC
Publication date 2014-12-08
ISSN 1526-4602
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Organic
Polymer Science
Summary 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.
Language eng
DOI 10.1021/bm501263s
Field of Research 030799 Theoretical and Computational Chemistry not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, American Chemical Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30069939

Document type: Journal Article
Collections: Institute for Frontier Materials
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