The N Terminus of Adhesion G Protein-Coupled Receptor GPR126/ADGRG6 as Allosteric Force Integrator.
The N Terminus of Adhesion G Protein-Coupled Receptor GPR126/ADGRG6 as Allosteric Force Integrator.
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DOI：
10.3389/fcell.2022.873278
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
粘附G蛋白偶联受体（aGPCR）GPR 126/ADGRG 6在几种生理功能中起重要作用，例如髓鞘形成或外周神经修复。这使得受体成为有吸引力的药理学靶标。GPR 126是一种机械传感器，将细胞外基质（ECM）分子与其N末端的结合转化为代谢性细胞内信号。迄今为止，这种ECM介导的受体活化所需的结构要求和力的性质在很大程度上是未知的。在这项研究中，我们通过将经典的第二信使检测与单细胞原子力显微镜相结合来提供这些信息。我们建立了一个单克隆抗体，靶向N端刺激GPR 126，并将其与通过其已知的ECM配体，胶原IV和层粘连蛋白211的激活进行比较。由于每个配体使用不同的作用模式，N末端可以被认为是一个变构模块，可以微调受体激活的上下文特异性的方式。
The adhesion G protein–coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the receptor an attractive pharmacological target. GPR126 is a mechano-sensor that translates the binding of extracellular matrix (ECM) molecules to its N terminus into a metabotropic intracellular signal. To date, the structural requirements and the character of the forces needed for this ECM-mediated receptor activation are largely unknown. In this study, we provide this information by combining classic second-messenger detection with single-cell atomic force microscopy. We established a monoclonal antibody targeting the N terminus to stimulate GPR126 and compared it to the activation through its known ECM ligands, collagen IV and laminin 211. As each ligand uses a distinct mode of action, the N terminus can be regarded as an allosteric module that can fine-tune receptor activation in a context-specific manner.
DOI：
10.2174/138620708784911465
发表时间：
2008-07
影响因子：
1.8
作者：
Gupta A;Heimann AS;Gomes I;Devi LA
通讯作者：
Devi LA