Characterization of parathyroid hormone/receptor interactions: structure of the first extracellular loop

Biochemistry. 2000 Jul 18;39(28):8153-60. doi: 10.1021/bi000196f.


The structural features of the first extracellular loop (ECL1) of the parathyroid hormone receptor (PTH1R) in the presence of dodecylphosphocholine micelles have been determined using high-resolution NMR techniques. The structure of the receptor fragment, PTH1R(241-285), includes three alpha-helices for residues 241-244, 256-264, and 275-284. The first and third correspond to the end and the beginning of transmembrane helices 2 and 3, respectively. Centrally located in the second helix is L(261), found to cross-link to Lys(27) of parathyroid hormone, PTH(1-34) [Greenberg, Z., Bisello, A., Mierke, D. F., Rosenblatt, M., and Chorev, M. (2000) Biochemistry 39, 8142-8152]. On the basis of nitroxide radical-induced relaxation studies, the central helix is found to associate with the surface of the membrane mimetic. These data, in conjunction with previous results indicating a preference of PTH for the lipid surface, suggest a membrane-associated pathway for the initial recognition and binding of PTH to its G-protein-coupled receptor. Using the structural features of ECL1 as determined here, along with the structure of the PTH(1-34), the intermolecular interactions consistent with the contact point between L(261)(receptor)-Lys(27)(ligand) are identified.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry
  • Micelles
  • Models, Chemical
  • Models, Molecular
  • Parathyroid Hormone / chemistry*
  • Parathyroid Hormone / metabolism
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Protein Conformation
  • Receptors, Parathyroid Hormone / chemistry*
  • Receptors, Parathyroid Hormone / metabolism


  • Membrane Proteins
  • Micelles
  • Parathyroid Hormone
  • Receptors, Parathyroid Hormone
  • Phosphorylcholine
  • dodecylphosphocholine