β-Hairpin Miniprotein Stabilization in Trehalose Glass Is Facilitated by an Emergent Compact Non-Native State

Gil I. Olgenblum, Frank Wien, Liel Sapir, Daniel Harries*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

From stem cell freeze-drying to organ storage, considerable recent efforts have been directed toward the development of new preservation technologies. A prominent protein stabilizing strategy involves vitrification in glassy matrices, most notably those formed of sugars such as the biologically relevant preservative trehalose. Here, we compare the folding thermodynamics of a model miniprotein in solution and in the glassy state of the sugars trehalose and glucose. Using synchrotron radiation circular dichroism (SRCD), we find that the same native structure persists in solution and glass. However, upon transition to the glass, a completely different, conformationally restricted unfolded state replaces the disordered denatured state found in solution, potentially inhibiting misfolding. Concomitantly, a large exothermic contribution is observed in glass, exposing the stabilizing effect of interactions with the sugar matrix on the native state. Our results shed light on the mechanism of protein stabilization in sugar glass and should aid in future preservation technologies.

Original languageAmerican English
Pages (from-to)7659-7664
Number of pages6
JournalJournal of Physical Chemistry Letters
Volume12
DOIs
StatePublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

Fingerprint

Dive into the research topics of 'β-Hairpin Miniprotein Stabilization in Trehalose Glass Is Facilitated by an Emergent Compact Non-Native State'. Together they form a unique fingerprint.

Cite this