Structural Plasticity of the Selectivity Filter in Cation Channels

Abstract

Ion channels allow for the passage of ions across biological membranes, which is essential for the functioning of a cell. In pore loop channels the selectivity filter (SF) is a conserved sequence that forms a constriction with multiple ion binding sites. It is becoming increasingly clear that there are several conformations and dynamic states of the SF in cation channels. Here we outline specific modes of structural plasticity observed in the SFs of various pore loop channels: disorder, asymmetry, and collapse. We summarize the multiple atomic structures with varying SF conformations as well as asymmetric and more dynamic states that were discovered recently using structural biology, spectroscopic, and computational methods. Overall, we discuss here that structural plasticity within the SF is a key molecular determinant of ion channel gating behavior.

Protein structure and dynamics in the era of integrative structural biology

“…Molecular chaperones (Margulies et al, 2022), molecular motors (Ariga et al, 2020), pores (Hendriks et al, 2021), transporters (Hou et al, 2022), and host proteins of membraneless organelles (Hardenberg et al, 2020) provide additional examples of the biological relevance of protein structural dynamics.…”