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Structure and Dynamics of the Active Human Parathyroid Hormone receptor-1

Structure and Dynamics of the Active Human Parathyroid Hormone receptor-1

Li-Hua Zhao, Shanshan Ma, Ieva Sutkeviciute, Dan-Dan Shen, X Edward Zhou, Parker W de Waal, Chen-Yao Li, Yanyong Kang, Lisa J Clark, Frederic G Jean-Alphonse, Alex D White, Dehua Yang, Antao Dai, Xiaoqing Cai, etc.

Science. 2019 Apr 12;364(6436):148-153.

PMID: 30975883

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417921	RPTPg Active human			Price
IAR4245700	PDE4A1A Active human			Price

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