Department of Biosystems Science and Engineering, ETH Zürich, Mattenstr. 26, 4058 Basel, Switzerland.
Structure. 2012 Aug 8;20(8):1391-402. doi: 10.1016/j.str.2012.05.010. Epub 2012 Jun 28.
G protein-coupled receptors (GPCRs) are a class of versatile proteins that transduce signals across membranes. Extracellular stimuli induce inter- and intramolecular interactions that change the functional state of GPCRs and activate intracellular messenger molecules. How these interactions are established and how they modulate the functional state of GPCRs remain to be understood. We used dynamic single-molecule force spectroscopy to investigate how ligand binding modulates the energy landscape of the human β2 adrenergic receptor (β2 AR). Five different ligands representing either agonists, inverse agonists or neutral antagonists established a complex network of interactions that tuned the kinetic, energetic, and mechanical properties of functionally important structural regions of β2 AR. These interactions were specific to the efficacy profile of the ligands investigated and suggest that the functional modulation of GPCRs follows structurally well-defined interaction patterns.
G 蛋白偶联受体（GPCRs）是一类多功能蛋白，能够跨膜传递信号。细胞外刺激诱导分子间和分子内相互作用，改变 GPCR 的功能状态并激活细胞内信使分子。这些相互作用是如何建立的，以及它们如何调节 GPCR 的功能状态，仍有待了解。我们使用动态单分子力谱技术研究了配体结合如何调节人β2 肾上腺素能受体（β2AR）的能量景观。五种不同的配体代表激动剂、反向激动剂或中性拮抗剂，建立了一个复杂的相互作用网络，调节了β2AR 中功能重要的结构区域的动力学、能量和机械性质。这些相互作用是针对所研究配体的效力谱特异性的，并表明 GPCR 的功能调节遵循结构上明确的相互作用模式。
