Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
Trends Biochem Sci. 2014 Dec;39(12):594-602. doi: 10.1016/j.tibs.2014.10.001. Epub 2014 Nov 4.
The discovery of biased signaling at G protein-coupled receptors (GPCRs), the largest class of cell surface receptors and primary drug targets for numerous human diseases, has redefined the classical concepts of receptor pharmacology. It not only highlights the depth of signaling diversity within the GPCR system, but also offers possibilities for novel and more-effective therapeutics. Here, we highlight the recent biophysical and structural advances in our understanding of ligand-receptor interactions and conformational changes in the receptors, which provide novel mechanistic insights into biased GPCR signaling. We also underline key aspects of GPCR-biased signaling that remain to be investigated in greater detail to develop a complete molecular understanding of this process and overall GPCR signaling.
G 蛋白偶联受体 (GPCRs) 是细胞表面受体中最大的一类，也是众多人类疾病的主要药物靶点，其偏向信号的发现重新定义了受体药理学的经典概念。这不仅突显了 GPCR 系统中信号传递多样性的深度，也为新型、更有效的治疗方法提供了可能。在此，我们重点介绍了近期在理解配体-受体相互作用和受体构象变化方面的生物物理和结构方面的进展，这些进展为偏向 GPCR 信号传递提供了新的机制见解。我们还强调了 GPCR 偏向信号传递中仍需更详细研究的关键方面，以深入了解这一过程和整体 GPCR 信号传递的分子机制。
