| Autor: |
Barreto CAV; 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., Vitorino JNM; BioSI─Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Reis PBPS; BioSI─Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Machuqueiro M; BioSI─Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Moreira IS; CNC─Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal.; Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal. |
| Abstrakt: |
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 2.50 residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) p K a calculation protocol. We observed consistent differences (1.3 p K units) for the macroscopic p K a values between the inactive and active states of the A2AR and B2AR receptors, indicating the protonation of Asp 2.50 during GPCR activation. This process seems to be specific and not conserved, as no differences were observed in the p K a values of the remaining receptors (CB1R, NT1R, and GHSR). |
