François Dehez
Laboratoire de Physique et Chimie Théoriques (LPCT), CNRS/Université de Lorraine UMR 7019, 54506, Vandœuvre-lès-Nancy
Lundi 25 juin à 14h (salle Magat) :
“Membrane protein structures obtained in non-native environments. Are they always relevant ?”
Résumé
Membrane proteins (MPs) perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. The extraction of MPs from their native environment is central to their biophysical characterization and three-dimensional structure of MPs available in the Protein Data Bank have been essentially obtained using various detergents. Studies have emphasized that such molecules may perturb the structure and modify the dynamics of MPs.[1,2] However, it remains challenging to determine whether these perturbations are negligible or could be responsible for misfolded conformations, altering the protein’s function. Here, I will show how molecular simulations together with biophysical techniques can be employed to assess the physiological relevance of MPs structures resolved in dodecylphosphocholine (DPC), a detergent mainly employed in NMR.[3-6]
References
[1] Cross, T. A. et al. ; Trends Biochem. Sci. 2011, 36, 117–125.
[2] Khelashvili, G. et al. ; J. Am. Chem. Soc. 2013, 135, 14266–14275.
[3] Zoonens, M. et a.l ; J. Am. Chem. Soc. 2013, 135, 15174-15182
[4] Dehez, F. et al. ; Biophys. J. 2017, 113, 2311-2315.
[5] Kurauskas, V. et al. ; J. Phys. Chem. Lett. 2018, 9, 933-938.
[6] Chipot, C. et al. ; Chem. Rev. 2018, 118, 3559-3607
