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Article Dans Une Revue eLife Année : 2022

Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation

Nicolai Tidemand Johansen
Tone Bengtsen
Frederik Grønbæk Tidemand
Martin Cramer Pedersen
Pie Huda
Jens Berndtsson
Nageshewar Rao Yepuri
Mark Sansom
Mikaela Rapp
Guido Pintacuda
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Résumé

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 Mg 2+ 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 Mg 2+ -bound closed structure nor the Mg 2+ -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 Mg 2+ . We propose that CorA must be in a dynamic equilibrium between different non-conducting states, both symmetric and asymmetric, regardless of bound Mg 2+ but that conducting states become more populated in Mg 2+ -free conditions. These properties are regulated by backbone dynamics and are key to understanding the functional regulation of CorA.
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Dates et versions

hal-03853045 , version 1 (29-11-2021)
hal-03853045 , version 2 (15-11-2022)

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Nicolai Tidemand Johansen, Marta Bonaccorsi, Tone Bengtsen, Andreas Haahr Larsen, Frederik Grønbæk Tidemand, et al.. Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation. eLife, 2022, 11, ⟨10.7554/eLife.71887⟩. ⟨hal-03853045v2⟩
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