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dc.contributor.authorNewby, Franciscoen
dc.contributor.authorde, Simone Alfonsoen
dc.contributor.authorYagi-Utsumi, Mahoen
dc.contributor.authorSalvatella, Xavieren
dc.contributor.authorDobson, Christopheren
dc.contributor.authorVendruscolo, Micheleen
dc.date.accessioned2015-10-21T16:10:19Z
dc.date.available2015-10-21T16:10:19Z
dc.date.issued2015-10-19en
dc.identifier.citationBiochemistry 2015 54(46): 6876–6886. doi:10.1021/acs.biochem.5b00670en
dc.identifier.issn0006-2960
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252363
dc.description.abstractResidual dipolar couplings (RDCs) and paramagnetic relaxation enhancements (PREs) have emerged as valuable parameters for defining the structures and dynamics of disordered proteins by nuclear magnetic resonance (NMR) spectroscopy. Procedures for their measurement, however, may lead to conformational perturbations because of the presence of the alignment media necessary for recording RDCs, or of the paramagnetic groups that must be introduced for measuring PREs. We discuss here experimental methods to quantify these effects by considering the case of the 40-residue isoform of the amyloid  peptide (A40), which is associated with Alzheimer's disease. By carrying out RDC measurements over a range of concentrations of given alignment media, we show that perturbations arising from transient binding of A40 can be identified, enabling appropriate corrections to be made. In addition, by using NMR experiments sensitive to long-range interactions we show that it is possible to identify relatively non-perturbing sites for attaching nitroxide radicals for PRE measurements. Thus, controlling the conformational perturbations introduced by RDC and PRE measurements should facilitate their use for the rigorous determination of the conformational properties of disordered proteins.
dc.languageEnglishen
dc.language.isoenen
dc.publisherACS
dc.titleStructure-Free Validation of RDC and PRE Measurements of Disordered Proteinsen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/acs.biochem.5b00670en
prism.endingPage6886
prism.publicationDate2015en
prism.publicationNameBiochemistryen
prism.startingPage6876
prism.volume54en
rioxxterms.versionofrecord10.1021/acs.biochem.5b00670en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-10-19en
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.identifier.eissn1520-4995
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (EP/K039520/1)
rioxxterms.freetoread.startdate2016-10-19


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