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. Attached Files Name Description MIMEType Size Downloads Title Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre Author(s) Brown,AH Rodger,PM Evans,JS 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 Chemistry EXCHANGE MOLECULAR-DYNAMICS PARALLEL TEMPERING SIMULATIONS BINDING PROTEIN CBP21 FREE-ENERGY LANDSCAPE REPLICA-EXCHANGE CALCIUM-CARBONATE ORGANIC MATRIX IN-VITRO EXPLICIT SOLVENT SHELL PROTEINS 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 Collection: Institute for Frontier Materials Related Links Link Description Connect to Elements publication management system Go to link with your DU access privileges   Connect to published version Go to link with your DU access privileges   Author URL Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Mon, 23 Feb 2015, 10:39:37 EST Mon, 23 Feb 2015, 10:41:00 EST Tue, 24 Feb 2015, 04:00:30 EST Fri, 20 Mar 2015, 05:07:36 EST Thu, 26 Mar 2015, 13:05:39 EST Thu, 26 Mar 2015, 13:06:26 EST Thu, 26 Mar 2015, 13:11:50 EST Wed, 01 Apr 2015, 10:33:55 EST Filtered Full Citation counts:   Cited 10 times in TR Web of Science Cited 11 times in Scopus Search Google Scholar Access Statistics: 145 Abstract Views, 1 File Downloads  -  Detailed Statistics Created: Mon, 23 Feb 2015, 10:41:00 EST

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