Over the years, the association of peptide ligands to Family B GPCRs (G-protein coupled receptors) has been characterized by a number of experimental and theoretical techniques. For the PTH (parathyroid hormone) ligand–receptor system, important insight has been provided by photoaffinity labelling experiments and the elucidation of direct contact points between ligand and receptor. Our research has focused on the structural elucidation of the receptor domains shown to be involved in the binding of PTH. Employing a combination of carefully designed receptor domains, solution-state NMR carried out in the presence of membrane mimetics and extensive computer simulations, we have obtained a well-resolved model of the ligand–receptor complex for PTH. Here, we review the development of this model and highlight some inherent limitations of the methods employed and their consequences on interpretation of the ligand–receptor model.
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August 2007
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Conference Article|
July 20 2007
Structural characterization of the parathyroid hormone receptor domains determinant for ligand binding
D.F. Mierke;
D.F. Mierke
1
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
1To whom correspondence should be addressed (email Dale_Mierke@brown.edu).
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L. Mao;
L. Mao
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
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M. Pellegrini;
M. Pellegrini
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
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A. Piserchio;
A. Piserchio
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
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J. Plati;
J. Plati
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
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N. Tsomaia
N. Tsomaia
1Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, U.S.A.
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Publisher: Portland Press Ltd
Received:
April 30 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 721–723.
Article history
Received:
April 30 2007
Citation
D.F. Mierke, L. Mao, M. Pellegrini, A. Piserchio, J. Plati, N. Tsomaia; Structural characterization of the parathyroid hormone receptor domains determinant for ligand binding. Biochem Soc Trans 1 August 2007; 35 (4): 721–723. doi: https://doi.org/10.1042/BST0350721
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