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Abraham-Nordling M, Persson B, Nordling E. Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues. BMC Res Notes. 2010;3:270doi: 10.1186/1756-0500-3-270.
Abraham-Nordling, M., Persson, B., & Nordling, E. (2010). Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues. BMC research notes, 3270. https://doi.org/10.1186/1756-0500-3-270
Abraham-Nordling, Mirna, et al. "Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues." BMC research notes vol. 3 (2010): 270. doi: https://doi.org/10.1186/1756-0500-3-270
Abraham-Nordling M, Persson B, Nordling E. Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues. BMC Res Notes. 2010 Oct 27;3:270. doi: 10.1186/1756-0500-3-270. PMID: 20979597; PMCID: PMC2991341.
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BMC Res Notes. 2010 Oct 27;3:270. doi: 10.1186/1756-0500-3-270.

Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues.

BMC research notes

Mirna Abraham-Nordling, Bengt Persson, Erik Nordling

Affiliations

  1. Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. [email protected].

PMID: 20979597 PMCID: PMC2991341 DOI: 10.1186/1756-0500-3-270

Abstract

BACKGROUND: We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions.

FINDINGS: In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation.

CONCLUSIONS: A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.

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