title: Structural insight into the binding complex: β-arrestin/CCR5 complex.
abstract: The chemokine receptor 5 (CCR5) belongs to the superfamily of serpentine G protein-coupled receptors (GPCRs). The DRY motif (Asp, Arg, Tyr) of the intracellular loop 2 (ICL2), which is highly conserved in the GPCRs has been shown to be essential for the stability of folding of CCR5 and the interaction with β-arrestin. But the molecular mechanism by which it recognizes and interacts with β-arrestin has not been elucidated. In the present study, we described the active state of the β-arrestin structure using normal mode analysis and characterized the binding cleft of CCR5-ICL2 with β-arrestin using SABRE© docking tool and molecular dynamics simulation. Based on our computational results, we proposed a mode of binding between the ICL2 loop of CCR5 and β-arrestin structure, and modeled the energetically stable β-arrestin/CCR5 complex. In view of CCR5's importance as a therapeutic target for the treatment of HIV, this observation provides novel insight into the β-arrestin/CCR5 pathway. As a result, the current computational study of the detailed β-arrestin/CCR5 binding complex could provide the rationale for the development of next generation of HIV peptide inhibitors as therapeutic agents.
authors.affiliation: a Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences , Tunis , Tunisia .
authors.forename: Nejla
authors.initials: N
authors.lastname: Stambouli
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dridi
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Wei
authors.forename: Asma
authors.initials: A
authors.lastname: Jlizi
authors.forename: Abderahmen
authors.initials: A
authors.lastname: Bouraoui
authors.forename: Amel Ben Ammar
authors.initials: AB
authors.lastname: Elgaaied
mesh_terms: D000595:Amino Acid Sequence; D019390:Arrestins / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; C584933:CCR5 protein, human; D019713:Receptors, CCR5; D000071557:beta-Arrestins