title: Exploring structure-function relationships between TRP and Kv channels.
abstract: The molecular mechanisms underlying the activation of Transient Receptor Potential (TRP) ion channels are poorly understood when compared to those of the voltage-activated potassium (Kv) channels. The architectural and pharmacological similarities between the members of these two families of channels suggest that their structure-function relationships may have common features. We explored this hypothesis by replacing previously identified domains and critical structural motifs of the membrane-spanning portions of Kv2.1 with corresponding regions of two TRP channels, TRPM8 and TRPV1. Our results show that the S3b-S4 paddle motif of Kv2.1, but not other domains, can be replaced by the analogous regions of both TRP channels without abolishing voltage-activation. In contrast, replacement of portions of TRP channels with those of Kv2.1 consistently yielded non-functional channels. Taken together, these results suggest that most structural elements within TRP channels and Kv channels are not sufficiently related to allow for the creation of hybrid channels.
authors.affiliation: Porter Neuroscience Research Center, Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health 35 Convent Drive, Bethesda, Maryland 20892, USA.
authors.forename: Jeet
authors.initials: J
authors.lastname: Kalia
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D011487:Protein Conformation; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship; D050051:Transient Receptor Potential Channels / Q000737:chemistry*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D050051:Transient Receptor Potential Channels