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N.T. Johansen, M. Bonaccorsi, T. Bengtsen, A.H. Larsen, F.G. Tidemand, M.C. Pedersen, P. Huda, J. Berndtsson, T. Darwish, N.R. Yepuri, A. Martel, T.G. Pomorski, A. Bertarello, M. SP Sansom, M. Rapp, R. Crehuet, T. Schubeis, K. Lindorff-Larsen, G. Pintacuda, and L. Arleth (2022).
Mg²⁺-dependent conformational equilibria in CorA and an integrated view on transport regulation.
eLife 11: e71887
doi: 10.7554/eLife.71887

The CorA family of proteins regulates the homeostasis of divalent metal ions in many bacteria, archaea, and eukaryotic mitochondria, making it an important target in the investigation of the mechanisms of transport and its functional regulation. Although numerous structures of open and closed channels are now available for the CorA family, the mechanism of the transport regulation remains elusive. Here, we investigated the conformational distribution and associated dynamic behaviour of the pentameric Mg²⁺ channel CorA at room temperature using small-angle neutron scattering (SANS) in combination with molecular dynamics (MD) simulations and solid-state nuclear magnetic resonance spectroscopy (NMR). We find that neither the Mg²⁺-bound closed structure nor the Mg²⁺-free open forms are sufficient to explain the average conformation of CorA. Our data support the presence of conformational equilibria between multiple states, and we further find a variation in the behaviour of the backbone dynamics with and without Mg²⁺. We propose that CorA must be in a dynamic equilibrium between different non-conducting states, both symmetric and asymmetric, regardless of bound Mg²⁺ but that conducting states become more populated in Mg²⁺-free conditions. These properties are regulated by backbone dynamics and are key to understanding the functional regulation of CorA.