Mechanistic Insights into Structural Stability of the Selectivity Filters in Typical Cation Channels — Oak Academic Publishing
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Mechanistic Insights into Structural Stability of the Selectivity Filters in Typical Cation Channels
Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
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Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
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Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
1 Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
2 Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
3 Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, State Key Laboratory of Mechanics and Control of Mechanical Structure, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China
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.
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