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J Phys Chem Lett. 2018 Mar 1;9(5):933-938. doi: 10.1021/acs.jpclett.8b00269. Epub 2018 Feb 8.

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

Author information

1
Université Grenoble Alpes, CNRS, CEA, IBS , 38000 Grenoble, France.
2
Department of Biological and Environmental Sciences and Technologies, University of Salento , 73100 Lecce, Italy.
3
MRC-MBU, University of Cambridge , Cambridge CB2 0XY, United Kingdom.
4
CNRS, INSERM, Université de Montpellier , 34094 Montpellier, France.
5
Dept of Pharmacy, University of Calabria , 87036 Arcavacata di Rende, Italy.
6
LPCT, UMR 7019 Université de Lorraine, CNRS and Laboratoire International Associé & University of Illinois at Urbana-Champaign , F-54500 Vandoeuvre-lès-Nancy, France.

Abstract

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.

PMID:
29397729
PMCID:
PMC5834942
DOI:
10.1021/acs.jpclett.8b00269
[Indexed for MEDLINE]
Free PMC Article

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