title: Absence of ion-binding affinity in the putatively inactivated low-[K+] structure of the KcsA potassium channel.
abstract: Potassium channels are membrane proteins that selectively conduct K(+) across cellular membranes. The narrowest part of their pore, the selectivity filter, is responsible for distinguishing K(+) from Na(+), and can also act as a gate through a mechanism known as C-type inactivation. It has been proposed that a conformation of the KcsA channel obtained by crystallization in presence of low concentration of K(+) (PDB 1K4D) could correspond to the C-type inactivated state. Here, we show using molecular mechanics simulations that such conformation has little ion-binding affinity and that ions do not contribute to its stability. The simulations suggest that, in this conformation, the selectivity filter is mostly occupied by water molecules. Whether such ion-free state of the KcsA channel is physiologically accessible and representative of the inactivated state of eukaryotic channels remains unclear.
authors.affiliation: Swiss Institute of Bioinformatics, Computational & Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Boiteux
authors.forename: Simon
authors.initials: S
authors.lastname: Bernèche
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012964:Sodium / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D014867:Water; D012964:Sodium; D011188:Potassium