Gating mechanism of CorA family membrane proteins

It is already a big challenge to caputre functional conformations of proteins. And it is even a greater challenge to capture the conformations of multimeric proteins!

I am happy to share that the results from a great PhD work of my student on the gating mechanism CorA family membrane protein channels has been published in JCIM!

Only after using Martini and Gō models we have obtained a complete picture of the complex conformational behaviour these multimeric proteins exhibit!

I think the abstract describes the main outcomes of the work very well:

The CorA family of proteins plays a housekeeping role in the homeostasis of divalent metal ions in many bacteria and archaea as well as in mitochondria of eukaryotes, rendering it an important target to study the mechanisms of divalent transport and regulation across different life domains. Despite numerous studies, the mechanistic details of the channel gating and the transport of the metal ions are still not entirely understood. Here, we use all-atom and coarse-grained molecular dynamics simulations combined with in vitro experiments to investigate the influence of divalent cations on the function of CorA. Simulations reveal pronounced asymmetric movements of monomers that enable the rotation of the α7 helix and the cytoplasmic subdomain with the subsequent formation of new interactions and the opening of the channel. These computational results are functionally validated using site-directed mutagenesis of the intracellular cytoplasmic domain residues and biochemical assays. The obtained results infer a complex network of interactions altering the structure of CorA to allow gating. Furthermore, we attempt to reconcile the existing gating hypotheses for CorA to conclude the mechanism of transport of divalent cations via these proteins.