title: Light on the structure of thromboxane A₂receptor heterodimers.
abstract: The structure-based design of a mutant form of the thromboxane A(2) prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the hetero-dimeric complexes between the TPα and β isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPα-TPβ hetero-dimerization serves to regulate TPα function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution.
authors.affiliation: Department of Chemistry, Dulbecco Telethon Institute, University of Modena and Reggio Emilia, via Campi 183, 41100 Modena, Italy. fanelli@unimo.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
authors.forename: Mario
authors.initials: M
authors.lastname: Mauri
authors.forename: Valérie
authors.initials: V
authors.lastname: Capra
authors.forename: Francesco
authors.initials: F
authors.lastname: Raimondi
authors.forename: Francesca
authors.initials: F
authors.lastname: Guzzi
authors.forename: Manuela
authors.initials: M
authors.lastname: Ambrosio
authors.forename: G Enrico
authors.initials: GE
authors.lastname: Rovati
authors.forename: Marco
authors.initials: M
authors.lastname: Parenti
mesh_terms: D002319:Cardiovascular System / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D031541:Fluorescence Resonance Energy Transfer; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000737:chemistry* / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D007295:Inositol Phosphates; D044244:Receptors, Thromboxane A2, Prostaglandin H2