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Download fileDangerous Liaisons between Detergents and Membrane Proteins. The Case of Mitochondrial Uncoupling Protein 2
journal contribution
posted on 2016-02-18, 16:56 authored by Manuela Zoonens, Jeffrey Comer, Sandrine Masscheleyn, Eva Pebay-Peyroula, Christophe Chipot, Bruno Miroux, François DehezThe
extraction of membrane proteins from their native environment
by detergents is central to their biophysical characterization. Recent
studies have emphasized that detergents may perturb the structure
locally and modify the dynamics of membrane proteins. However, it
remains challenging to determine whether these perturbations are negligible
or could be responsible for misfolded conformations, altering the
protein’s function. In this work, we propose an original strategy
combining functional studies and molecular simulations to address
the physiological relevance of membrane protein structures obtained
in the presence of detergents. We apply our strategy to a structure
of isoform 2 of an uncoupling protein (UCP2) binding an inhibitor
recently obtained in dodecylphosphocholine detergent micelles. Although
this structure shares common traits with the ADP/ATP carrier, a member
of the same protein family, its functional and biological significance
remains to be addressed. In the present investigation, we demonstrate
how dodecylphosphocholine severely alters the structure as well as
the function of UCPs. The proposed original strategy opens new vistas
for probing the physiological relevance of three-dimensional structures
of membrane proteins obtained in non-native environments.