Journal of Cardiovascular Pharmacology ( IF 3 ) Pub Date : 2022-09-01 , DOI: 10.1097/fjc.0000000000001185 Laura M Wingler 1 , Andrew P Feld
Understanding the activation of G protein-coupled receptors (GPCRs) is of paramount importance to the field of cardiovascular medicine due to the critical physiological roles of these receptors and their prominence as drug targets. Although many cardiovascular GPCRs have been extensively studied as model receptors for decades, new complexities in their regulation continue to emerge. As a result, there is an ongoing need to develop novel approaches to monitor and to modulate GPCR activation. In less than a decade, nanobodies, or recombinant single-domain antibody fragments from camelids, have become indispensable tools for interrogating GPCRs both in purified systems and in living cells. Nanobodies have gained traction rapidly due to their biochemical tractability and their ability to recognize defined states of native proteins. Here, we review how nanobodies have been adopted to elucidate the structure, pharmacology, and signaling of cardiovascular GPCRs, resolving long-standing mysteries and revealing unexpected mechanisms. We also discuss how advancing technologies to discover nanobodies with tailored specificities may expand the impact of these tools for both basic science and therapeutic applications.
中文翻译:
纳米抗体作为心血管 G 蛋白偶联受体的探针和调节剂
了解 G 蛋白偶联受体 (GPCR) 的激活对于心血管医学领域至关重要,因为这些受体的关键生理作用及其作为药物靶点的突出地位。尽管几十年来许多心血管 GPCR 作为模型受体被广泛研究,但其调控的新复杂性不断出现。因此,持续需要开发新的方法来监测和调节 GPCR 激活。在不到十年的时间里,纳米抗体或来自骆驼科动物的重组单域抗体片段已成为在纯化系统和活细胞中检测 GPCR 不可或缺的工具。纳米抗体因其生化易处理性和识别天然蛋白质定义状态的能力而迅速获得关注。这里,我们回顾了如何采用纳米抗体来阐明心血管 GPCR 的结构、药理学和信号传导,解决长期存在的谜团并揭示意想不到的机制。我们还讨论了发现具有定制特异性的纳米抗体的先进技术如何扩大这些工具对基础科学和治疗应用的影响。