The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas
The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas
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DOI：
10.1016/j.jmb.2006.12.043
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发表时间：
2007-03-23
影响因子：
5.6
通讯作者：
Sato, Chikara
中科院分区：
文献类型：
--
作者：
Mio, Kazuhiro;Ogura, Toshihiko;Sato, Chikara
瞬时受体电位 (TRP) 通道是内在传感器，适用于响应来自细胞内部和外部的各种刺激。在 TRP 超家族中，经典的 TRP-3 (TRPC3) 已被广泛研究，并参与各种生物过程，如神经元分化、血管收缩和免疫细胞成熟。在刺激与磷脂酶 C 连接的表面膜受体后，TRPC3 介导细胞外 Ca2+ 跨膜流入，以控制 Ca2+ 信号传导，与内部储存的 Ca2+ 释放相一致。然而，人们对 TRP 超家族的结构基础知之甚少。在这里，我们展示了 15 埃分辨率的 TRPC3 结构。 TRP 超家族的第一个 3D 描述是根据冷冻电子显微镜获得的 135,909 个粒子图像重建的。大的细胞内域代表了“嵌套盒”结构：线框外壳可用作激活剂和调节剂的传感器，而球状内室可以调节离子流，因为它沿着中心轴与致密的跨膜核心串联排列。跨膜结构域表现出成孔特性。这种结构意味着 TRP 超家族已经多样化地进化为专门用于各种信号的传感器，而不是简单的离子传导装置。 (c) 2007 Elsevier Ltd. 保留所有权利。
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 angstrom 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. (c) 2007 Elsevier Ltd. All rights reserved.