6FJ3

High resolution crystal structure of parathyroid hormone 1 receptor in complex with a peptide agonist.

Summary for 6FJ3

• Entry DOI: 10.2210/pdb6fj3/pdb
• Descriptor: Parathyroid hormone/parathyroid hormone-related peptide receptor,Parathyroid hormone/parathyroid hormone-related peptide receptor,GlgA glycogen synthase,Parathyroid hormone/parathyroid hormone-related peptide receptor, CHLORIDE ION, Parathyroid hormone, ... (11 entities in total)
• Functional Keywords: gpcr, cell signalling, 7tm, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 78576.89

Authors

Ehrenmann, J.,Schoppe, J.,Klenk, C.,Rappas, M.,Kummer, L.,Dore, A.S.,Pluckthun, A. (deposition date: 2018-01-19, release date: 2018-11-21, Last modification date: 2024-01-17)

Primary citation

Ehrenmann, J.,Schoppe, J.,Klenk, C.,Rappas, M.,Kummer, L.,Dore, A.S.,Pluckthun, A.
High-resolution crystal structure of parathyroid hormone 1 receptor in complex with a peptide agonist.
Nat. Struct. Mol. Biol., 25:1086-1092, 2018

PubMed Abstract: Parathyroid hormone 1 receptor (PTH1R) is a class B multidomain G-protein-coupled receptor (GPCR) that controls calcium homeostasis. Two endogenous peptide ligands, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), activate the receptor, and their analogs teriparatide and abaloparatide are used in the clinic to increase bone formation as an effective yet costly treatment for osteoporosis. Activation of PTH1R involves binding of the peptide ligand to the receptor extracellular domain (ECD) and transmembrane domain (TMD), a hallmark of class B GPCRs. Here, we present the crystal structure of human PTH1R in complex with a peptide agonist at 2.5-Å resolution, allowing us to delineate the agonist binding mode for this receptor and revealing molecular details within conserved structural motifs that are critical for class B receptor function. Thus, this study provides structural insight into the function of PTH1R and extends our understanding of this therapeutically important class of GPCRs.

PubMed: 30455434
DOI: 10.1038/s41594-018-0151-4

Experimental method

X-RAY DIFFRACTION (2.5 Å)