Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Deparment of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Structure. 2014 Feb 4;22(2):260-8. doi: 10.1016/j.str.2013.11.008. Epub 2013 Dec 26.
Transient receptor potential (TRP) proteins are a large family of polymodal nonselective cation channels. The TRP vanilloid (TRPV) subfamily consists of six homologous members with diverse functions. TRPV1-TRPV4 are nonselective cation channels proposed to play a role in nociception, while TRPV5 and TRPV6 are involved in epithelial Ca²⁺ homeostasis. Here we present the cryo-electron microscopy (cryo-EM) structure of functional, full-length TRPV2 at 13.6 Å resolution. The map reveals that the TRPV2 cytoplasmic domain displays a 4-fold petal-like shape in which high-resolution N-terminal ankyrin repeat domain (ARD) structures can be unambiguously fitted. Fitting of the available ARD structures for other TRPV subfamily members into the TRPV2 EM map suggests that TRPV subfamily members have highly homologous structural topologies. These results allowed us to postulate a structural explanation for the functional diversity among TRPV channels and their differential regulation by proteins and ligands.
瞬时受体电位（TRP）蛋白是一大类多模式非选择性阳离子通道。TRP 香草素（TRPV）亚家族由六个具有不同功能的同源成员组成。TRPV1-TRPV4 是非选择性阳离子通道，据推测在痛觉中起作用，而 TRPV5 和 TRPV6 则参与上皮细胞 Ca²⁺稳态。在这里，我们展示了功能完整全长 TRPV2 的冷冻电镜（cryo-EM）结构，分辨率为 13.6Å。该图谱显示，TRPV2 细胞质结构域呈 4 倍花瓣状，其中可以明确拟合高分辨率 N 端锚蛋白重复结构域（ARD）结构。将其他 TRPV 亚家族成员的可用 ARD 结构拟合到 TRPV2 的 EM 图谱中表明， TRPV 亚家族成员具有高度同源的结构拓扑。这些结果使我们能够对 TRPV 通道之间的功能多样性及其受蛋白质和配体的差异调节提出结构解释。
