title: Molecular bases of multimodal regulation of a fungal transient receptor potential (TRP) channel.
abstract: Multimodal activation by various stimuli is a fundamental characteristic of TRP channels. We identified a fungal TRP channel, TRPGz, exhibiting activation by hyperosmolarity, temperature increase, cytosolic Ca(2+) elevation, membrane potential, and H2O2 application, and thus it is expected to represent a prototypic multimodal TRP channel. TRPGz possesses a cytosolic C-terminal domain (CTD), primarily composed of intrinsically disordered regions with some regulatory modules, a putative coiled-coil region and a basic residue cluster. The CTD oligomerization mediated by the coiled-coil region is required for the hyperosmotic and temperature increase activations but not for the tetrameric channel formation or other activation modalities. In contrast, the basic cluster is responsible for general channel inhibition, by binding to phosphatidylinositol phosphates. The crystal structure of the presumed coiled-coil region revealed a tetrameric assembly in an offset spiral rather than a canonical coiled-coil. This structure underlies the observed moderate oligomerization affinity enabling the dynamic assembly and disassembly of the CTD during channel functions, which are compatible with the multimodal regulation mediated by each functional module.
authors.affiliation: Molecular Signaling Research Team, Structural Physiology Research Group, RIKEN SPring-8 Center, Sayo, Hyogo 679-5148, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Shin
authors.initials: S
authors.lastname: Hamamoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyanoiri
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takeda
authors.forename: Masatsune
authors.initials: M
authors.lastname: Kainosho
authors.forename: Isamu
authors.initials: I
authors.lastname: Yabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Uozumi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamashita
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005874:Gibberella / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D050052:TRPC Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D050052:TRPC Cation Channels; D002118:Calcium
keywords: Analytical Ultracentrifugation; Calcium Intracellular Release; Coiled-coil; Crystal Structure; Ion Channels; NMR; Phosphatidylinositol Signaling; TRP Channel; Whole-vacuole Patch Clamp Recording
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