β                         2                         -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide

Sylwia Berbeć; Robert Dec; Dmitry Molodenskiy; Beata Wielgus-Kutrowska; Christian Johannessen; Agnieszka Hernik-Magoń; Fernando Tobias; Agnieszka Bzowska; Grzegorz Ścibisz; Timothy A. Keiderling; Dmitri Svergun; Wojciech Dzwolak

doi:10.1021/acs.jpcb.8b08308

β ₂ -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide

Sylwia Berbeć, Robert Dec, Dmitry Molodenskiy, Beata Wielgus-Kutrowska, Christian Johannessen, Agnieszka Hernik-Magoń, Fernando Tobias, Agnieszka Bzowska, Grzegorz Ścibisz, Timothy A. Keiderling, Dmitri Svergun, Wojciech Dzwolak^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	11895-11905
Number of pages	11
Journal	Journal of Physical Chemistry B
Volume	122
Issue number	50
DOIs	https://doi.org/10.1021/acs.jpcb.8b08308
State	Published - Dec 20 2018

Funding

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.

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Surfaces, Coatings and Films
Materials Chemistry

Access to Document

10.1021/acs.jpcb.8b08308

Cite this

Berbeć, S., Dec, R., Molodenskiy, D., Wielgus-Kutrowska, B., Johannessen, C., Hernik-Magoń, A., Tobias, F., Bzowska, A., Ścibisz, G., Keiderling, T. A., Svergun, D., & Dzwolak, W. (2018). β ₂ -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide. Journal of Physical Chemistry B, 122(50), 11895-11905. https://doi.org/10.1021/acs.jpcb.8b08308

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title = "β 2 -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide",

abstract = " 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.",

author = "Sylwia Berbe{\'c} and Robert Dec and Dmitry Molodenskiy and Beata Wielgus-Kutrowska and Christian Johannessen and Agnieszka Hernik-Mago{\'n} and Fernando Tobias and Agnieszka Bzowska and Grzegorz {\'S}cibisz and Keiderling, \{Timothy A.\} and Dmitri Svergun and Wojciech Dzwolak",

note = "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: {\textcopyright} Copyright 2018 American Chemical Society.",

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doi = "10.1021/acs.jpcb.8b08308",

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Berbeć, S, Dec, R, Molodenskiy, D, Wielgus-Kutrowska, B, Johannessen, C, Hernik-Magoń, A, Tobias, F, Bzowska, A, Ścibisz, G, Keiderling, TA, Svergun, D & Dzwolak, W 2018, 'β ₂ -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide', Journal of Physical Chemistry B, vol. 122, no. 50, pp. 11895-11905. https://doi.org/10.1021/acs.jpcb.8b08308

β ₂ -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide. / Berbeć, Sylwia; Dec, Robert; Molodenskiy, Dmitry et al.
In: Journal of Physical Chemistry B, Vol. 122, No. 50, 20.12.2018, p. 11895-11905.

Research output: Contribution to journal › Article › peer-review

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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Berbeć S, Dec R, Molodenskiy D, Wielgus-Kutrowska B, Johannessen C, Hernik-Magoń A et al. β ₂ -Type Amyloidlike Fibrils of Poly- l -glutamic Acid Convert into Long, Highly Ordered Helices upon Dissolution in Dimethyl Sulfoxide. Journal of Physical Chemistry B. 2018 Dec 20;122(50):11895-11905. doi: 10.1021/acs.jpcb.8b08308