Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region
Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region
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DOI：
10.1074/jbc.c800040200
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发表时间：
2008-06-27
影响因子：
4.8
通讯作者：
Miyano, Masashi
中科院分区：
文献类型：
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作者：
Shimamura, Tatsuro;Hiraki, Kenji;Miyano, Masashi
g蛋白偶联受体通过g蛋白转导各种细胞外信号，在细胞信号转导级联反应中起关键作用。视紫红质是一种典型的g蛋白偶联受体，参与视网膜视觉信号级联。我们在3.7 A分辨率下确定了鱿鱼视紫红质的结构，它通过G(q)蛋白将信号转导到磷酸肌醇级联。该结构具有7个跨膜螺旋和一个两亲螺旋H8，其几何结构与牛视紫红质偶联G(t)和人β(2)-肾上腺素能受体偶联G(s)的结构相似。值得注意的是，鱿鱼视紫红质含有一个结构良好的细胞质区域，参与与g蛋白的相互作用，这个区域在牛视紫红质和人β 2-肾上腺素能受体中是灵活的或紊乱的。跨膜螺旋5和6较长并突出到细胞质中。远端c端尾部在棕榈酰化半胱氨酸残基后含有一个短的亲水α -螺旋CH。远端c端尾部的残基与相邻的第二个细胞质环、挤出的跨膜螺旋5和6以及短螺旋H8中的残基相互作用。此外，Tyr-111、Asn-87和Asn-185残基位于席夫碱氮原子的氢键距离内。
G-protein-coupled receptors play a key step in cellular signal transduction cascades by transducing various extracellular signals via G-proteins. Rhodopsin is a prototypical G-protein-coupled receptor involved in the retinal visual signaling cascade. We determined the structure of squid rhodopsin at 3.7 A resolution, which transduces signals through the G(q) protein to the phosphoinositol cascade. The structure showed seven transmembrane helices and an amphipathic helix H8 has similar geometry to structures from bovine rhodopsin, coupling to G(t), and human beta(2)-adrenergic receptor, coupling to G(s). Notably, squid rhodopsin contains a well structured cytoplasmic region involved in the interaction with G-proteins, and this region is flexible or disordered in bovine rhodopsin and human beta 2-adrenergicreceptor. The transmembrane helices 5 and 6 are longer and extrude into the cytoplasm. The distal C-terminal tail contains a short hydrophilic alpha-helix CH after the palmitoylated cysteine residues. The residues in the distal C-terminal tail interact with the neighboring residues in the second cytoplasmic loop, the extruded transmembrane helices 5 and 6, and the short helix H8. Additionally, the Tyr-111, Asn-87, and Asn-185 residues are located within hydrogen-bonding distances from the nitrogen atom of the Schiff base.