TITLE:
Mechanistic Insights into Structural Stability of the Selectivity Filters in Typical Cation Channels
AUTHORS:
Zhoubin Tang, Hu Qiu, Wanlin Guo
KEYWORDS:
Ion Channel, Structural Stability, Molecular Dynamics, Electrostatic Potential, Hydrogen Bonds
JOURNAL NAME:
Journal of Materials Science and Chemical Engineering,
Vol.10 No.7,
July
29,
2022
ABSTRACT:
The reliable functioning of ion channels should be closely related to their structural stability. The selectivity filter in the KcsA potassium channel possesses four stable ion binding sites that can coordinate nearly fully dehydrated ions, whereas only two of such binding sites exist in the non-selective NaK channel, and none of them is found in the NavAb sodium channel. Here we show that the stability of the selectivity filters in these tetrameric cation channels is inversely correlated with the number of stable binding sites by extensive molecular dynamics simulations. While the presence of coordinated ions is crucial for the selectivity filters of the KcsA and NaK channels to stabilize the conformations in their crystal structures, the selectivity filter of the NavAb channel shows higher stability, independent of the presence of ions. We further show that the distinct repulsive electrostatic interactions between negatively charged oxygen atoms in the selectivity filter which form the stable binding sites are responsible for the different stability of these cation channels. The hydrogen bonding networks between residues in the selectivity filter and its adjacent pore helix also play an important role in maintaining stability. Together, these results provide important mechanistic insights into the structural stability of the selectivity filters in typical cation channels.