title: Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer.
abstract: A strong interplay between the voltage-sensor domain (VSD) and the pore domain (PD) underlies voltage-gated channel functions. In a few voltage-sensitive proteins, the VSD has been shown to function without a canonical PD, although its structure and oligomeric state remain unknown. Here, using EPR spectroscopy, we show that the isolated VSD of KvAP can remain monomeric in a reconstituted bilayer and retain a transmembrane conformation. We find that water-filled crevices extending deep into the membrane around S3, a scaffold conducive to transport of protons/cations, are intrinsic to the VSD. Differences in solvent accessibility in comparison to the full-length KvAP allowed us to define an interacting footprint of the PD on the VSD. This interaction is centered around S1 and S2 and suggests a rotation of 70 degrees -100 degrees relative to Kv1.2-Kv2.1 chimera. Sequence-conservation patterns in Kv channels, Hv channels, and voltage-sensitive phosphatases reveal several near-universal features suggesting a common molecular architecture for all VSDs.
authors.affiliation: Institute for Biophysical Dynamics, Center for Integrative Science, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Chakrapani
authors.forename: Luis G
authors.initials: LG
authors.lastname: Cuello
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
mesh_terms: D000595:Amino Acid Sequence; D015640:Ion Channel Gating / Q000502:physiology*; D051663:Kv1.2 Potassium Channel / Q000737:chemistry; D008051:Lipid Bilayers / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D051663:Kv1.2 Potassium Channel; D008051:Lipid Bilayers; D024642:Potassium Channels, Voltage-Gated