TY - JOUR
T1 - β 2 -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide
AU - Berbeć, Sylwia
AU - Dec, Robert
AU - Molodenskiy, Dmitry
AU - Wielgus-Kutrowska, Beata
AU - Johannessen, Christian
AU - Hernik-Magoń, Agnieszka
AU - Tobias, Fernando
AU - Bzowska, Agnieszka
AU - Ścibisz, Grzegorz
AU - Keiderling, Timothy A.
AU - Svergun, Dmitri
AU - Dzwolak, Wojciech
N1 - Funding Information:
This work was supported by the National Science Centre of Poland, grant no. DEC-2011/03/B/ST4/03063 and, in part, by the BST program (W.D.) of the Department of Chemistry, University of Warsaw. The study was carried out at the Biological and Chemical Research Centre, University of Warsaw, established within the project cofinanced by EU from the European Regional Development Fund under the Operational Programme Innovative Economy, 2007−2013. D.M. and also SAXS experiments at EMBL Hamburg were supported by iNEXT project, grant number 653706, funded by the Horizon 2020 programme of the European Commission. The AUC experiments were performed in the NanoFun laboratories cofinanced by the ERDF Project POIG.02.02.00-00-025/09. The University of Ghent (IOF Advanced TT) is acknowledged for the purchase of ChiralRAMAN-2X. We are grateful to Heng Chi for help with spectroscopic measurements.
Publisher Copyright:
© Copyright 2018 American Chemical Society.
PY - 2018/12/20
Y1 - 2018/12/20
N2 - Replacing water with dimethyl sulfoxide (DMSO) completely reshapes the free-energy landscapes of solvated proteins. In DMSO, a powerful hydrogen-bond (HB) acceptor, formation of HBs between backbone NH groups and solvent is favored over HBs involving protein's carbonyl groups. This entails a profound structural disruption of globular proteins and proteinaceous aggregates (e.g., amyloid fibrils) upon transfer to DMSO. Here, we investigate an unusual DMSO-induced conformational transition of β 2 -amyloid fibrils from poly-l-glutamic acid (PLGA). The infrared spectra of β 2 -PLGA dissolved in DMSO lack the typical features associated with disordered conformation that are observed when amyloid fibrils from other proteins are dispersed in DMSO. Instead, the frequency and unusual narrowness of the amide I band imply the presence of highly ordered helical structures, which is supported by complementary methods, including vibrational circular dichroism and Raman optical activity. We argue that the conformation most consistent with the spectroscopic data is that of a PLGA chain essentially lacking nonhelical segments such as bends that would provide DMSO acceptors with direct access to the backbone. A structural study of DMSO-dissolved β 2 -PLGA by synchrotron small-angle X-ray scattering reveals the presence of long uninterrupted helices lending direct support to this hypothesis. Our study highlights the dramatic effects that solvation may have on conformational transitions of large polypeptide assemblies.
AB - Replacing water with dimethyl sulfoxide (DMSO) completely reshapes the free-energy landscapes of solvated proteins. In DMSO, a powerful hydrogen-bond (HB) acceptor, formation of HBs between backbone NH groups and solvent is favored over HBs involving protein's carbonyl groups. This entails a profound structural disruption of globular proteins and proteinaceous aggregates (e.g., amyloid fibrils) upon transfer to DMSO. Here, we investigate an unusual DMSO-induced conformational transition of β 2 -amyloid fibrils from poly-l-glutamic acid (PLGA). The infrared spectra of β 2 -PLGA dissolved in DMSO lack the typical features associated with disordered conformation that are observed when amyloid fibrils from other proteins are dispersed in DMSO. Instead, the frequency and unusual narrowness of the amide I band imply the presence of highly ordered helical structures, which is supported by complementary methods, including vibrational circular dichroism and Raman optical activity. We argue that the conformation most consistent with the spectroscopic data is that of a PLGA chain essentially lacking nonhelical segments such as bends that would provide DMSO acceptors with direct access to the backbone. A structural study of DMSO-dissolved β 2 -PLGA by synchrotron small-angle X-ray scattering reveals the presence of long uninterrupted helices lending direct support to this hypothesis. Our study highlights the dramatic effects that solvation may have on conformational transitions of large polypeptide assemblies.
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U2 - 10.1021/acs.jpcb.8b08308
DO - 10.1021/acs.jpcb.8b08308
M3 - Article
C2 - 30427196
AN - SCOPUS:85058076114
SN - 1520-6106
VL - 122
SP - 11895
EP - 11905
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 50
ER -