G protein-coupled receptors (GPCRs) are membrane proteins that traverse the plasma membrane seven times (hence, are also called 7TM receptors). The polytopic structure of GPCRs makes the folding of GPCRs difficult and complex. Indeed, many wild-type GPCRs are not folded optimally, and defects in folding are the most common cause of genetic diseases due to GPCR mutations. Both general and receptor-specific molecular chaperones aid the folding of GPCRs. Chemical chaperones have been shown to be able to correct the misfolding in mutant GPCRs, proving to be important tools for studying the structure-function relationship of GPCRs. However, their potential therapeutic value is very limited. Pharmacological chaperones (pharmacoperones) are potentially important novel therapeutics for treating genetic diseases caused by mutations in GPCR genes that resulted in misfolded mutant proteins. Pharmacoperones also increase cell surface expression of wild-type GPCRs; therefore, they could be used to treat diseases that do not harbor mutations in GPCRs. Recent studies have shown that indeed pharmacoperones work in both experimental animals and patients. High-throughput assays have been developed to identify new pharmacoperones that could be used as therapeutics for a number of endocrine and other genetic diseases.

中文翻译：

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陪伴 G 蛋白偶联受体：从细胞生物学到治疗学。

G 蛋白偶联受体 (GPCR) 是一种膜蛋白，可穿过质膜七次（因此也称为 7TM 受体）。GPCR 的多面体结构使 GPCR 的折叠变得困难和复杂。事实上，许多野生型 GPCR 并未最佳折叠，折叠缺陷是 GPCR 突变导致遗传疾病的最常见原因。一般分子伴侣和受体特异性分子伴侣都有助于 GPCR 的折叠。化学伴侣已被证明能够纠正突变 GPCR 中的错​​误折叠，证明是研究 GPCR 结构-功能关系的重要工具。然而，它们的潜在治疗价值非常有限。药理学伴侣 (pharmacoperones) 是治疗由 GPCR 基因突变导致错误折叠突变蛋白引起的遗传疾病的潜在重要新疗法。药效酮还可增加野生型 GPCR 的细胞表面表达；因此，它们可用于治疗不包含 GPCR 突变的疾病。最近的研究表明，药效酮确实对实验动物和患者都有效。已经开发出高通量测定来鉴定可用作许多内分泌和其他遗传疾病治疗剂的新药效酮。最近的研究表明，药效酮确实对实验动物和患者都有效。已经开发出高通量测定来鉴定可用作许多内分泌和其他遗传疾病治疗剂的新药效酮。最近的研究表明，药效酮确实对实验动物和患者都有效。已经开发出高通量测定来鉴定可用作许多内分泌和其他遗传疾病治疗剂的新药效酮。