3L2J
Dimeric structure of the ligand-free extracellular domain of the human parathyroid hormone receptor (PTH1R)
Summary for 3L2J
| Entry DOI | 10.2210/pdb3l2j/pdb |
| Related | 3C4M 3H3G |
| Related PRD ID | PRD_900001 |
| Descriptor | Fusion protein of Maltose-binding periplasmic protein and Parathyroid hormone/parathyroid hormone-related peptide receptor, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose (2 entities in total) |
| Functional Keywords | dimer, extracellular domain, mbp fusion protein, periplasm, sugar transport, transport, cell membrane, disease mutation, disulfide bond, dwarfism, g-protein coupled receptor, glycoprotein, membrane, receptor, transducer, transmembrane, membrane protein |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 2 |
| Total formula weight | 120391.27 |
| Authors | Pioszak, A.A.,Xu, H.E. (deposition date: 2009-12-15, release date: 2010-02-02, Last modification date: 2024-11-06) |
| Primary citation | Pioszak, A.A.,Harikumar, K.G.,Parker, N.R.,Miller, L.J.,Xu, H.E. Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J.Biol.Chem., 285:12435-12444, 2010 Cited by PubMed Abstract: The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an alpha-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein. PubMed: 20172855DOI: 10.1074/jbc.M109.093138 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.24 Å) |
Structure validation
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