The mechanism of denaturation and the unfolded state of the α-helical membrane-associated protein Mistic

Tomas Jacso, Benjamin Bardiaux, Jana Broecker, Sebastian Fiedler, Tom Baerwinkel, Andi Mainz, Uwe Fink, Carolyn Vargas, Hartmut Oschkinat, Sandro Keller, Bernd Reif

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

In vitro protein-folding studies using chemical denaturants such as urea are indispensible in elucidating the forces and mechanisms determining the stability, structure, and dynamics of water-soluble proteins. By contrast, α-helical membrane-associated proteins largely evade such approaches because they are resilient to extensive unfolding. We have used optical and NMR spectroscopy to provide an atomistic-level dissection of the effects of urea on the structure and dynamics of the α-helical membrane-associated protein Mistic as well as its interactions with detergent and solvent molecules. In the presence of the zwitterionic detergent lauryl dimethylamine oxide, increasing concentrations of urea result in a complex sequence of conformational changes that go beyond simple two-state unfolding. Exploiting this finding, we report the first high-resolution structural models of the urea denaturation process of an α-helical membrane-associated protein and its completely unfolded state, which contains almost no regular secondary structure but nevertheless retains a topology close to that of the folded state.

Original languageEnglish
Pages (from-to)18884-18891
Number of pages8
JournalJournal of the American Chemical Society
Volume135
Issue number50
DOIs
StatePublished - 18 Dec 2013

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