Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains.

Stefania A Mari, João Pessoa, Stephen Altieri, Ulf Hensen, Lise Thomas, João H Morais-Cabral, Daniel J Müller

Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, 4058 Basel, Switzerland.

Proceedings of the National Academy of Sciences of the United States of America 2011 Dec 20

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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.

Citation

Stefania A Mari, João Pessoa, Stephen Altieri, Ulf Hensen, Lise Thomas, João H Morais-Cabral, Daniel J Müller. Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains. Proceedings of the National Academy of Sciences of the United States of America. 2011 Dec 20;108(51):20802-7