PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, Portugal.
CNC─Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal.
J Chem Inf Model. 2024 Sep 9;64(17):6850-6856. doi: 10.1021/acs.jcim.4c01125. Epub 2024 Aug 16.
The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal in helping to understand their activation process. However, the role of protonation-conformation coupling in GPCR activation still needs to be clarified. We studied the protonation behavior of the highly conserved Asp residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) p calculation protocol. We observed consistent differences (1.3 p units) for the macroscopic p values between the inactive and active states of the A2AR and B2AR receptors, indicating the protonation of Asp during GPCR activation. This process seems to be specific and not conserved, as no differences were observed in the p values of the remaining receptors (CB1R, NT1R, and GHSR).
可用 G 蛋白偶联受体 (GPCR) 结构的增加在帮助理解其激活过程方面发挥了关键作用。然而，质子化构象偶联在 GPCR 激活中的作用仍需阐明。我们使用线性响应近似 (LRA) p 计算方案研究了五个不同 A 类 GPCR（活性和非活性构象）中高度保守的 Asp 残基的质子化行为。我们观察到 A2AR 和 B2AR 受体的无活性和活性状态之间的宏观 p 值存在一致差异（1.3 p 单位），表明 GPCR 激活过程中 Asp 的质子化。这个过程似乎是特异性的，而不是保守的，因为在其余受体（CB1R、NT1R 和 GHSR）的 p 值中没有观察到差异。
