Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity

Handle URI:
http://hdl.handle.net/10754/599114
Title:
Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity
Authors:
Reymer, Anna; Frederick, Kendra K.; Rocha, Sandra; Beke-Somfai, Tamás; Kitts, Catherine C.; Lindquist, Susan; Nordén, Bengt
Abstract:
Structural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional structural-biology methods. We investigate two different phenotypic prion strains, weak and strong, of yeast translation termination factor Sup35 with respect to angular orientation of tyrosines using polarized light spectroscopy. By applying a combination of alignment methods the degree of fiber orientation can be assessed, which allows a relatively accurate determination of the aromatic ring angles. Surprisingly, the strains show identical average orientations of the tyrosines, which are evenly spread through the amyloid core. Small variations between the two strains are related to the local environment of a fraction of tyrosines outside the core, potentially reflecting differences in fibril packing.
Citation:
Reymer A, Frederick KK, Rocha S, Beke-Somfai T, Kitts CC, et al. (2014) Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity. Proc Natl Acad Sci USA 111: 17158–17163. Available: http://dx.doi.org/10.1073/pnas.1415663111.
Publisher:
Proceedings of the National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences
KAUST Grant Number:
KUK-11-008-23
Issue Date:
17-Nov-2014
DOI:
10.1073/pnas.1415663111
PubMed ID:
25404291
PubMed Central ID:
PMC4260602
Type:
Article
ISSN:
0027-8424; 1091-6490
Sponsors:
This work was supported by King Abdullah University of Science and Technology Grant KUK-11-008-23, European Research Council Grant EC-2008 AdG 227700-SUMO, Swedish Research Council Linnaeus Grant SUPRA 349-2007-8680, Howard Hughes Medical Institute (HHMI), and National Institutes of Health Grant GM025874 (to S.L.). K.K.F. was an HHMI Fellow of the Life Science Research Foundation.
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Full metadata record

DC FieldValue Language
dc.contributor.authorReymer, Annaen
dc.contributor.authorFrederick, Kendra K.en
dc.contributor.authorRocha, Sandraen
dc.contributor.authorBeke-Somfai, Tamásen
dc.contributor.authorKitts, Catherine C.en
dc.contributor.authorLindquist, Susanen
dc.contributor.authorNordén, Bengten
dc.date.accessioned2016-02-25T13:53:08Zen
dc.date.available2016-02-25T13:53:08Zen
dc.date.issued2014-11-17en
dc.identifier.citationReymer A, Frederick KK, Rocha S, Beke-Somfai T, Kitts CC, et al. (2014) Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity. Proc Natl Acad Sci USA 111: 17158–17163. Available: http://dx.doi.org/10.1073/pnas.1415663111.en
dc.identifier.issn0027-8424en
dc.identifier.issn1091-6490en
dc.identifier.pmid25404291en
dc.identifier.doi10.1073/pnas.1415663111en
dc.identifier.urihttp://hdl.handle.net/10754/599114en
dc.description.abstractStructural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional structural-biology methods. We investigate two different phenotypic prion strains, weak and strong, of yeast translation termination factor Sup35 with respect to angular orientation of tyrosines using polarized light spectroscopy. By applying a combination of alignment methods the degree of fiber orientation can be assessed, which allows a relatively accurate determination of the aromatic ring angles. Surprisingly, the strains show identical average orientations of the tyrosines, which are evenly spread through the amyloid core. Small variations between the two strains are related to the local environment of a fraction of tyrosines outside the core, potentially reflecting differences in fibril packing.en
dc.description.sponsorshipThis work was supported by King Abdullah University of Science and Technology Grant KUK-11-008-23, European Research Council Grant EC-2008 AdG 227700-SUMO, Swedish Research Council Linnaeus Grant SUPRA 349-2007-8680, Howard Hughes Medical Institute (HHMI), and National Institutes of Health Grant GM025874 (to S.L.). K.K.F. was an HHMI Fellow of the Life Science Research Foundation.en
dc.publisherProceedings of the National Academy of Sciencesen
dc.subjectTyrosineen
dc.subjectPolarized lighten
dc.subjectLinear Dichroismen
dc.subjectPrion Proteinsen
dc.subjectSup35 Strainsen
dc.subject.meshProtein Structure, Tertiaryen
dc.titleOrientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversityen
dc.typeArticleen
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.identifier.pmcidPMC4260602en
dc.contributor.institutionDepartment of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden; reymer@chalmers.se norden@chalmers.se.en
dc.contributor.institutionWhitehead Institute for Biomedical Research, Cambridge, MA 02142; and Howard Hughes Medical Institute and.en
dc.contributor.institutionDepartment of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden;en
dc.contributor.institutionWhitehead Institute for Biomedical Research, Cambridge, MA 02142; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.en
kaust.grant.numberKUK-11-008-23en

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