How Detergent Impacts Membrane Proteins: Atomic-Level Views of Mitochondrial Carriers in Dodecylphosphocholine.

TitleHow Detergent Impacts Membrane Proteins: Atomic-Level Views of Mitochondrial Carriers in Dodecylphosphocholine.
Publication TypeJournal Article
Year of Publication2018
AuthorsKurauskas, V, Hessel, A, Ma, P, Lunetti, P, Weinhäupl, K, Imbert, L, Brutscher, B, King, MS, Sounier, R, Dolce, V, Kunji, ERS, Capobianco, L, Chipot, C, Dehez, F, Bersch, B, Schanda, P
JournalJ Phys Chem Lett
Date Published2018 Mar 01
KeywordsDetergents, Micelles, Mitochondrial ADP, ATP Translocases, Mitochondrial Membrane Transport Proteins, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Phosphorylcholine, Protein Conformation, Protein Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins

Characterizing the structure of membrane proteins (MPs) generally requires extraction from their native environment, most commonly with detergents. Yet, the physicochemical properties of detergent micelles and lipid bilayers differ markedly and could alter the structural organization of MPs, albeit without general rules. Dodecylphosphocholine (DPC) is the most widely used detergent for MP structure determination by NMR, but the physiological relevance of several prominent structures has been questioned, though indirectly, by other biophysical techniques, e.g., functional/thermostability assay (TSA) and molecular dynamics (MD) simulations. Here, we resolve unambiguously this controversy by probing the functional relevance of three different mitochondrial carriers (MCs) in DPC at the atomic level, using an exhaustive set of solution-NMR experiments, complemented by functional/TSA and MD data. Our results provide atomic-level insight into the structure, substrate interaction and dynamics of the detergent-membrane protein complexes and demonstrates cogently that, while high-resolution NMR signals can be obtained for MCs in DPC, they systematically correspond to nonfunctional states.

Alternate JournalJ Phys Chem Lett
Citation Key10.1021/acs.jpclett.8b00269
PubMed ID29397729
PubMed Central IDPMC5834942
Grant List311318 / / European Research Council / International
MC_U105663139 / / Medical Research Council / United Kingdom