Decoding Partner Specificity of Opioid Receptor Family.

Autor: Barreto CAV; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., Baptista SJ; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.; Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, University of Coimbra, Coimbra, Portugal., Preto AJ; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal., Silvério D; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal., Melo R; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.; Department of Life Sciences, University of Coimbra, Coimbra, Portugal., Moreira IS; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Jazyk: angličtina
Zdroj: Frontiers in molecular biosciences [Front Mol Biosci] 2021 Sep 21; Vol. 8, pp. 715215. Date of Electronic Publication: 2021 Sep 21 (Print Publication: 2021).
DOI: 10.3389/fmolb.2021.715215
Abstrakt: This paper describes an exciting big data analysis compiled in a freely available database, which can be applied to characterize the coupling of different G-Protein coupled receptors (GPCRs) families with their intracellular partners. Opioid receptor (OR) family was used as case study in order to gain further insights into the physiological properties of these important drug targets, known to be associated with the opioid crisis, a huge socio-economic issue directly related to drug abuse. An extensive characterization of all members of the ORs family ( μ (MOR), δ (DOR), κ (KOR), nociceptin (NOP)) and their corresponding binding partners (ARRs: Arr2, Arr3; G-protein: G i1 , G i2 , G i3 , G o , G ob , G z , G q , G 11 , G 14 , G 15 , G 12 , G ssh , G slo ) was carried out. A multi-step approach including models' construction (multiple sequence alignment, homology modeling), complex assembling (protein complex refinement with HADDOCK and complex equilibration), and protein-protein interface characterization (including both structural and dynamics analysis) were performed. Our database can be easily applied to several GPCR sub-families, to determine the key structural and dynamical determinants involved in GPCR coupling selectivity.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Barreto, Baptista , Preto, Silvério, Melo and Moreira.)
Databáze: MEDLINE
Externí odkaz: