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Theoretical Computational and Biophysics Group - "Dangerous liaisons between detergents and membrane proteins. The case of mitochondrial uncoupling protein 2."

Event Type
Klaus Schulten - TCB Group
3269 Beckman Institute
Oct 11, 2013   1:00 pm  
Dr. Francois Dehez, Nancy University, Vandoeuvre-les-Nancy, France
Originating Calendar
Physics - Theoretical Biophysics Seminar

The extraction of membrane proteins from their native environment by detergents is central for their biophysical characterization. Recent studies have emphasized that detergents may perturb the structure


locally and modify the dynamics of membrane proteins.

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. 4

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 5

demonstrate how dodecylphosphocholine severely alters the structure as well as the function of UCP. The proposed strategy opens new vistas for probing the physiological relevance of three-dimensional structures of membrane proteins obtained in non-native environments.

(1) Cross, T. A.; Sharma, M.; Yi, M.; Zhou, H.-X. Trends Biochem. Sci. 2011, 36, 117–125. (2) Khelashvili, G.; LeVine, M. V.; Shi, L.; Quick, M.; Javitch, J. A.; Weinstein, H. J. Am. Chem. Soc. 2013, 135, 14266– 14275.
(3) Berardi, M. J.; Shih, W. M.; Harrison, S. C.; Chou, J. J. Nature 2011, 476, 109–113. (4) Pebay- Peyroula, E.; Dahout-Gonzalez, C.; Kahn, R.; Trézéguet, V.; Lauquin, G. J.-M.; Brandolin, G. Nature 2003, 426, 39–44.
(5) Zoonens, M.; Comer, J.; Masscheleyn, S.; Pebay-Peyroula, E.; Chipot, C.; Miroux, B.; Dehez, F. J. Am. Chem. Soc. 2013, DOI: 10.1021/ja407424v.

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