title: Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains.
abstract: Cyclic nucleotide-regulated ion channels are present in bacteria, plants, vertebrates, and humans. In higher organisms, they are closely involved in signaling networks of vision and olfaction. Binding of cAMP or cGMP favors the activation of these ion channels. Despite a wealth of structural and studies, there is a lack of structural data describing the gating process in a full-length cyclic nucleotide-regulated channel. We used high-resolution atomic force microscopy (AFM) to directly observe the conformational change of the membrane embedded bacterial cyclic nucleotide-regulated channel MlotiK1. In the nucleotide-bound conformation, the cytoplasmic cyclic nucleotide-binding (CNB) domains of MlotiK1 are disposed in a fourfold symmetric arrangement forming a pore-like vestibule. Upon nucleotide-unbinding, the four CNB domains undergo a large rearrangement, stand up by ∼1.7 nm, and adopt a structurally variable grouped conformation that closes the cytoplasmic vestibule. This fully reversible conformational change provides insight into how CNB domains rearrange when regulating the potassium channel.
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, 4058 Basel, Switzerland.
authors.forename: Stefania A
authors.initials: SA
authors.lastname: Mari
authors.forename: João
authors.initials: J
authors.lastname: Pessoa
authors.forename: Stephen
authors.initials: S
authors.lastname: Altieri
authors.forename: Ulf
authors.initials: U
authors.lastname: Hensen
authors.forename: Lise
authors.initials: L
authors.lastname: Thomas
authors.forename: João H
authors.initials: JH
authors.lastname: Morais-Cabral
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry; D059128:Mesorhizobium / Q000378:metabolism*; D018625:Microscopy, Atomic Force / Q000379:methods; D009154:Mutation; D009712:Nucleotides, Cyclic / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D008563:Membrane Lipids; D009712:Nucleotides, Cyclic; D015221:Potassium Channels; D000242:Cyclic AMP