Structural and Functional Characterization of a Calcium-Activated Cation Channel From Tsukamurella Paurometabola

Abstract

The selectivity filter is an essential functional element of K þ channels that is highly conserved both in terms of its primary sequence and its three-dimensional structure. Here, we investigate the properties of an ion channel from the Gram-positive bacterium Tsukamurella paurometabola with a selectivity filter formed by an uncommon proline-rich sequence. Electrophysiological recordings show that it is a non-selective cation channel and that its activity depends on Ca 2 þ concentration. In the crystal structure, the selectivity filter adopts a novel conformation with Ca 2 þ ions bound within the filter near the pore helix where they are coordinated by backbone oxygen atoms, a recurrent motif found in multiple proteins. The binding of Ca 2 þ ion in the selectivity filter controls the widening of the pore as shown in crystal structures and in molecular dynamics simulations. The structural, functional and computational data provide a characterization of this calcium-gated cationic channel.

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways

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Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation

“…Despite the complications associated with parameterization of polarizable force fields, and higher computational overhead for MD runs, hybrid polarizable/additive and fully polarizable models have been used for prototypical gramicidin A ion channel simulations Patel et al 2009;Vorobyov et al 2010;Peng et al 2016), demonstrating reduced free energy barriers and thus providing more accurate channel conductance. And, fully polarizable MD simulations were reported recently for other ion channels as well (Dhakshnamoorthy et al 2016;Kratochvil et al 2016;Sun & Gong, 2017).…”

“…And, fully polarizable MD simulations were reported recently for other ion channels as well (Dhakshnamoorthy et al . ; Kratochvil et al . ; Sun & Gong, ).…”

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