The TRPC3 Channel Has a Large Internal Chamber Surrounded by Signal Sensing Antennas

Transient receptor potential (TRP) channels are intrinsic sensors adapted for response to all manner of stimuli both from inside and from outside the cell. Within the TRP superfamily, the canonical TRP-3 (TRPC3) has been widely studied and is involved in various biological processes such as neuronal...

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Bibliographic Details
Published in:Journal of molecular biology 2007-03, Vol.367 (2), p.373-383
Main Authors: Mio, Kazuhiro, Ogura, Toshihiko, Kiyonaka, Shigeki, Hiroaki, Yoko, Tanimura, Yukihiro, Fujiyoshi, Yoshinori, Mori, Yasuo, Sato, Chikara
Format: Article
Language:English
Subjects:
Binding Sites
calcium signaling
Cell Line
Cell Membrane - chemistry
cryo-electron microscopy
Cryoelectron Microscopy
Humans
Models, Molecular
Protein Conformation
single-particle analysis
transient receptor potential
TRPC Cation Channels - chemistry
TRPC3
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Summary:Transient receptor potential (TRP) channels are intrinsic sensors adapted for response to all manner of stimuli both from inside and from outside the cell. Within the TRP superfamily, the canonical TRP-3 (TRPC3) has been widely studied and is involved in various biological processes such as neuronal differentiation, blood vessel constriction, and immune cell maturation. Upon stimulation of surface membrane receptors linked to phospholipase C, TRPC3 mediates transmembrane Ca2+ influx from outside the cell to control Ca2+ signaling, in concert with the Ca2+ release from internal stores. The structural basis of TRP superfamily has, however, been poorly understood. Here we present a structure of the TRPC3 at 15 Å resolution. This first 3D depiction of TRP superfamily was reconstructed from 135,909 particle images obtained with cryo-electron microscopy. The large intracellular domain represents a “nested-box” structure: a wireframe outer shell is functionable as sensors for activators and modulators, and a globular inner chamber may modulate ion flow, since it is aligned tandem along the central axis with the dense membrane-spanning core. The transmembrane domain demonstrates a pore-forming property. This structure implies that the TRP superfamily has diversely evolved as sensors specialized for various signals, rather than as simple ion-conducting apparatuses.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2006.12.043