The extracellular amino-terminal region of the parathyroid hormone (PTH)/PTH-related peptide receptor determines the binding affinity for carboxyl-terminal fragments of PTH-(1-34)

Endocrinology. 1994 Feb;134(2):879-84. doi: 10.1210/endo.134.2.8299582.


The recombinant human PTH/PTH-related peptide (PTHrP) receptor, when transiently expressed in COS-7 cells, binds [Nle8,18,Tyr34] bovine PTH-(7-34)amide [PTH-(7-34)], human PTH-(10-34)amide [PTH-(10-34)], and bovine PTH-(15-34)amide [PTH-(15-34)] with at least 50-fold higher affinity than does the rat receptor homolog. In contrast, PTH-(1-34) binding affinities are similar for both receptor homologs. To map those areas of the PTH/PTHrP receptors that determine the binding specificity for carboxyl-terminal fragments of PTH-(1-34), we constructed chimeric rat/human PTH/PTHrP receptors. These bound PTH-(1-34) with normal affinity and, therefore, must have an overall conformation that resembles that of native receptors. Chimeras with the amino-terminal extracellular domain of the human PTH/PTHrP receptor have a considerably higher binding affinity for PTH-(7-34), PTH-(10-34), and PTH-(15-34) than do the reciprocal receptor constructs in which the amino-terminal region is from the rat PTH/PTHrP receptor. The opossum PTH/PTHrP receptor homolog also binds PTH-(7-34) with higher affinity than the rat receptor, and studies of rat/opossum chimeras confirm the importance of the amino-terminal extracellular domain in determining the PTH-(7-34) binding specificity. Mutant rat and human PTH/PTHrP receptors in which either residues 61-105 of the extracellular region or most of the intracellular tail were deleted have PTH-(7-34) binding characteristics indistinguishable from those of either wild-type receptor. These findings indicate that the amino-terminal extracellular region of the PTH/PTHrP receptor contains a domain(s) that largely determines the binding affinity of amino-terminally truncated PTH analogs. This region, therefore, is likely to constitute a site for ligand-receptor interaction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cattle
  • Cell Line
  • Chlorocebus aethiops
  • Gene Expression
  • Humans
  • Kidney
  • Kinetics
  • Mutagenesis, Site-Directed
  • Parathyroid Hormone / metabolism*
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments / metabolism*
  • Protein Conformation
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / metabolism
  • Protein Structure, Secondary
  • Proteins / metabolism*
  • Rats
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone / chemistry
  • Receptors, Parathyroid Hormone / metabolism*
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Teriparatide
  • Transfection


  • PTHLH protein, human
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Protein Sorting Signals
  • Proteins
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone
  • Recombinant Proteins
  • Teriparatide