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Light on the structure of thromboxane A2 receptor heterodimers

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Abstract

The structure-based design of a mutant form of the thromboxane A2 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.

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Acknowledgments

This work was supported by grants from the Telethon-Italy Grant No. S00068TELU to F.F., the Italian Ministry for University and Research (MiUR-FIRB Grant No. RBIN04CKYN) to M.P., and from European Community Framework Program 6 (No. LSHM-CT-2004-005033) and Fondazione Banca del Monte di Lombardia to G.E.R.

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Authors and Affiliations

  1. Department of Chemistry, Dulbecco Telethon Institute, University of Modena and Reggio Emilia, via Campi 183, 41100, Modena, Italy

    Francesca Fanelli

  2. Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy

    Francesca Fanelli & Francesco Raimondi

  3. Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy

    Mario Mauri, Francesca Guzzi & Marco Parenti

  4. Laboratory of Molecular Pharmacology, Department of Pharmacological Sciences, University of Milano, Milan, Italy

    Valérie Capra, Manuela Ambrosio & G. Enrico Rovati

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  1. Francesca Fanelli
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Correspondence to Francesca Fanelli.

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Fanelli, F., Mauri, M., Capra, V. et al. Light on the structure of thromboxane A2 receptor heterodimers. Cell. Mol. Life Sci. 68, 3109–3120 (2011). https://doi.org/10.1007/s00018-010-0615-0

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