CryoEM and MD infer water-mediated proton transport and autoinhibition mechanisms of VO complex. Rotary motor V-ATPases drive trans-membrane proton transport through a VO proton channel subcomplex. Despite recent high-resolution structures of several rotary ATPases, the dynamic mechanism of proton pumping remains elusive. Here, we have determined a 2.7 Å cryoEM structure of yeast VO proton channel in nanodisc that reveals the location of ordered water molecules along the proton path, as well as details of specific protein-lipid interactions and the architecture of the membrane scaffold protein. We also uncover a state of VO that shows the ten membrane-embedded c-ring proteins rotated by ~14º. Molecular dynamics simulations demonstrate that the two rotary states are in thermal equilibrium, and depict how the protonation state of essential glutamic acid residues in the proton path couples water mediated proton transfer with c-ring rotation. Our cryoEM models and simulations rationalize a mechanism for inhibition of passive proton transport as observed for free VO that is generated as a result of V-ATPase regulation by reversible disassembly in vivo. Science Advances, 2020.

Recent publications

Standard Binding Free Energy and Membrane Desorption Mechanism for a Phospholipase C
Emmanuel E. Moutoussamy; Hanif M. Khan; Mary F. Roberts; Anne Gershenson; Christophe Chipot; Nathalie Reuter;
Journal of Chemical Information and Modeling (2022)
MLCV: Bridging Machine-Learning-Based Dimensionality Reduction and Free-Energy Calculation
Haochuan Chen; Han Liu; Heying Feng; Haohao Fu; Wensheng Cai; Xueguang Shao; Christophe Chipot;
Journal of Chemical Information and Modeling (2022) 62 (1): 1-8
Conformational transitions and ligand-binding to a muscle-type nicotinic acetylcholine receptor
Eleftherios Zarkadas; Eva Pebay-Peyroula; Mackenzie John Thompson; Guy Schoehn; Tomasz Uchanski; Jan Steyaert; Christophe Chipot; Francois Dehez; John Edward Baenziger; Hugues Nury;
Neuron (2022) 7 (8): e42166-1370.e5


- Renewal of the Laboratoire International Associé CNRS-University of Illinois at Urbana-Champaign on November 2016
- An update of ParseFEP is available in the latest version of VMD.
- 新的分子动力学讲义 (Dissemination).


Laboratoire International Associé
Unité mixte de recherche n°7019
Université de Lorraine, B.P. 70239
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