Mitochondrial ADP/ATP Carrier in Dodecylphosphocholine Binds Cardiolipins with Non-native Affinity.

TitleMitochondrial ADP/ATP Carrier in Dodecylphosphocholine Binds Cardiolipins with Non-native Affinity.
Publication TypeJournal Article
Year of Publication2017
AuthorsDehez, F, Schanda, P, King, MS, Kunji, ERS, Chipot, C
JournalBiophys J
Volume113
Issue11
Pagination2311-2315
Date Published2017 Dec 05
ISSN1542-0086
KeywordsCardiolipins, Mitochondria, Mitochondrial ADP, ATP Translocases, Phosphorylcholine, Protein Binding
Abstract

Biophysical investigation of membrane proteins generally requires their extraction from native sources using detergents, a step that can lead, possibly irreversibly, to protein denaturation. The propensity of dodecylphosphocholine (DPC), a detergent widely utilized in NMR studies of membrane proteins, to distort their structure has been the subject of much controversy. It has been recently proposed that the binding specificity of the yeast mitochondrial ADP/ATP carrier (yAAC3) toward cardiolipins is preserved in DPC, thereby suggesting that DPC is a suitable environment in which to study membrane proteins. In this communication, we used all-atom molecular dynamics simulations to investigate the specific binding of cardiolipins to yAAC3. Our data demonstrate that the interaction interface observed in a native-like environment differs markedly from that inferred from an NMR investigation in DPC, implying that in this detergent, the protein structure is distorted. We further investigated yAAC3 solubilized in DPC and in the milder dodecylmaltoside with thermal-shift assays. The loss of thermal transition observed in DPC confirms that the protein is no longer properly folded in this environment.

DOI10.1016/j.bpj.2017.09.019
Alternate JournalBiophys. J.
Citation Key10.1016/j.bpj.2017.09.019
PubMed ID29056231
PubMed Central IDPMC5722206