Structure and dynamics of a multidomain ligand-gated ion channel revealed under acidic conditions

Ligand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. The bacterial channel DeCLIC constitutes a provocative model system for structure, function, and dynamics in this family, including a modulatory N-terminal domain (NTD). Previous closed structures of DeCLIC support a rationale for its inhibition by calcium; however, properties of its open state remain unclear. Here we used cryogenic electron microscopy under acidic conditions to determine a previously unreported conformation of DeCLIC with an expanded pore. This structure was relatively stable and permeable in simulations, and agreed with the average low-pH solution structure by small-angle neutron scattering. In the absence of calcium, an alternative closed class exhibited dynamic rearrangements in the NTD. We propose that our expanded-pore structure corresponds to a functional open state of DeCLIC, while calcium-site and NTD dynamics drive channel closure, providing a detailed template for modulatory mechanisms in the larger channel family.