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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors
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Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors

机译：代谢型谷氨酸受体5的庚型结构域的行为类似于视紫红质样受体

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摘要

Although agonists bind directly in the heptahelical domain (HD) of most class-l rhodopsin-like G protein coupled receptors (GPCRs), class-Ill agonists bind in the extracellular domain of their receptors. Indeed, the latter possess a large extracellular domain composed of a cysteine-rich domain and a Venus flytrap module. Both the low sequence homology and the structural organization of class-Ill GPCRs raised the question of whether or not the HD of these receptors functions the same way as rhodopsin-like GPCRs. Here, we show that the HD of metabotropic glutamate receptor 5 (mGlu_5) displays the same agonist-independent constitutive activity as the wild-type receptor. Moreover, we show that the non-competitive antagonist MPEP [2-methyl-6-(phenylethynyl)-pyri-dine hydrochloride] and the positive allosteric modulator DFB (3,3'-difluorobenzaldazine) act as inverse agonist and full agonist, respectively, on the mGlu_5 HD in the absence of the extracellular domain. This finding illustrates that, like rhodopsin-like receptors, the HD of mGluRs can constitutively couple to G proteins and be negatively and positively regulated by ligands. These data show that the HD of mGluRs behave like any other class-l GPCRs in terms of G protein coupling and regulation by various types of ligands.
机译：尽管激动剂直接结合在大多数I类视紫红质样G蛋白偶联受体（GPCR）的七螺旋结构域（HD）中，但III类激动剂却结合在其受体的细胞外结构域中。实际上，后者具有由富含半胱氨酸的结构域和维纳斯捕蝇器模块组成的大型胞外结构域。低序列同源性和III类GPCR的结构组织都提出了这些受体的HD是否以与视紫红质样GPCR相同的方式起作用的问题。在这里，我们显示代谢型谷氨酸受体5（mGlu_5）的高清显示与野生型受体相同的激动剂非依赖性组成性活性。此外，我们表明，非竞争性拮抗剂MPEP [2-甲基-6-（苯基乙炔基）-吡啶盐酸盐]和正构构调节剂DFB（3,3'-difluorobenzaldazine）分别充当反向激动剂和完全激动剂。 ，在缺少细胞外结构域的mGlu_5 HD上。这一发现说明，与视紫红质样受体一样，mGluR的HD可以与G蛋白组成性偶联，并受到配体的负调控。这些数据表明，mGluR的HD在G蛋白偶联和各种配体调控方面表现得与任何其他I类GPCR相似。

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