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

Research output: Contribution to journalArticlepeer-review

6 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 languageEnglish (US)
Pages (from-to)11895-11905
Number of pages11
JournalJournal of Physical Chemistry B
Volume122
Issue number50
DOIs
StatePublished - Dec 20 2018

ASJC Scopus subject areas

  • Materials Chemistry
  • Surfaces, Coatings and Films
  • Physical and Theoretical Chemistry

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