TRPC3 is a key player in many cellular functions, controlling growth cone guidance and synaptic plasticity in the central nervous system, blood vessel constriction , and the differentiation of immune cells. Mutations of this protein are implicated in various cardiovascular and kidney diseases.
Abstract from: Journal of Molecular Biology. Volume 367, Issue 2, 23 March 2007, Pages 373-383
Kazuhiro Mio, Toshihiko Ogura, Shigeki Kiyonaka, Yoko Hiroaki, Yukihiro Tanimura, Yoshinori Fujiyoshi, Yasuo Mori and Chikara Sato
Neuroscience Research Institute and Biological Information Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-4 Umezono, Tsukuba 305-8568, Japan.
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.