TY - JOUR

T1 - Mg2+-dependent conformational equilibria in CorA and an integrated view on transport regulation

AU - Johansen, Nicolai Tidemand

AU - Bonaccorsi, Marta

AU - Bengtsen, Tone

AU - Larsen, Andreas Haahr

AU - Tidemand, Frederik Grønbæk

AU - Pedersen, Martin Cramer

AU - Huda, Pie

AU - Berndtsson, Jens

AU - Darwish, Tamim

AU - Yepuri, Nageshewar Rao

AU - Martel, Anne

AU - Pomorski, Thomas Günther

AU - Bertarello, Andrea

AU - Sansom, Mark

AU - Rapp, Mikaela

AU - Crehuet, Ramon

AU - Schubeis, Tobias

AU - Lindorff-Larsen, Kresten

AU - Pintacuda, Guido

AU - Arleth, Lise

N1 - Publisher Copyright: © 2022, Johansen et al.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - cora mg2+ channel

KW - E. coli

KW - metadynamics simulation

KW - molecular biophysics

KW - small-angle neutron scattering

KW - solid-state nuclear magnetic resonance

KW - structural biology

U2 - 10.7554/eLife.71887

DO - 10.7554/eLife.71887

M3 - Journal article

C2 - 35129435

AN - SCOPUS:85125020573

VL - 11

JO - eLife

JF - eLife

SN - 2050-084X

ER -