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Structure paper

TitleStructure and dynamics of the active human parathyroid hormone receptor-1.
Journal, issue, pagesScience, Vol. 364, Issue 6436, Page 148-153, Year 2019
Publish dateApr 12, 2019
AuthorsLi-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 / Jian Chen / Cong Li / Yi Jiang / Tomoyuki Watanabe / Thomas J Gardella / Karsten Melcher / Ming-Wei Wang / Jean-Pierre Vilardaga / H Eric Xu / Yan Zhang /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:30975883 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 4.0 Å
Structure data

0410

6nbf

EMDB-0410, PDB-6nbf:
Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein
Method: EM (single particle) / Resolution: 3.0 Å

0411

6nbh

EMDB-0411, PDB-6nbh:
Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein
Method: EM (single particle) / Resolution: 3.5 Å

0412

6nbi

EMDB-0412, PDB-6nbi:
Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • homo sapiens (human)
  • bos taurus (cattle)
  • rattus norvegicus (Norway rat)
  • synthetic construct (others)
KeywordsSIGNALING PROTEIN / Parathyroid hormone receptor / GPCR / Class B GPCR / GPCR-G protein complex

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