6NBH

Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein

Summary for 6NBH

• Entry DOI: 10.2210/pdb6nbh/pdb
• EMDB information: 0411
• Descriptor: Parathyroid hormone/parathyroid hormone-related peptide receptor, Long-acting parathyroid hormone analog, Gs protein alpha subunit, ... (8 entities in total)
• Functional Keywords: parathyroid hormone receptor, gpcr, class b gpcr, gpcr-g protein complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 165860.57

Authors

Zhao, L.-H.,Ma, S.,Sutkeviciute, I.,Shen, D.-D.,Zhou, X.E.,de Waal, P.P.,Li, C.-Y.,Kang, Y.,Clark, L.J.,Jean-Alphonse, F.G.,White, A.D.,Xiao, K.,Yang, D.,Jiang, Y.,Watanabe, T.,Gardella, T.J.,Melcher, K.,Wang, M.-W.,Vilardaga, J.-P.,Xu, H.E.,Zhang, Y. (deposition date: 2018-12-07, release date: 2019-04-17, Last modification date: 2024-10-16)

Primary citation

Zhao, L.H.,Ma, S.,Sutkeviciute, I.,Shen, D.D.,Zhou, X.E.,de Waal, P.W.,Li, C.Y.,Kang, Y.,Clark, L.J.,Jean-Alphonse, F.G.,White, A.D.,Yang, D.,Dai, A.,Cai, X.,Chen, J.,Li, C.,Jiang, Y.,Watanabe, T.,Gardella, T.J.,Melcher, K.,Wang, M.W.,Vilardaga, J.P.,Xu, H.E.,Zhang, Y.
Structure and dynamics of the active human parathyroid hormone receptor-1.
Science, 364:148-153, 2019

PubMed Abstract: The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation.

PubMed: 30975883
DOI: 10.1126/science.aav7942

Experimental method

ELECTRON MICROSCOPY (3.5 Å)