6NBI

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


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

Structure and dynamics of the active human parathyroid hormone receptor-1.

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.

(2019) Science 364: 148-153

  • DOI: 10.1126/science.aav7942
  • Primary Citation of Related Structures:  

  • 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 b ...

    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.


    Organizational Affiliation

    The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Parathyroid hormone/parathyroid hormone-related peptide receptor
R
478Homo sapiensMutation(s): 1 
Gene Names: PTH1R (PTHR, PTHR1)
Find proteins for Q03431 (Homo sapiens)
Go to Gene View: PTH1R
Go to UniProtKB:  Q03431
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
Long-acting parathyroid hormone analog
P
36N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
Gs protein alpha subunit
A
378N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Entity ID: 4
MoleculeChainsSequence LengthOrganismDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
B
345Rattus norvegicusMutation(s): 0 
Gene Names: Gnb1
Find proteins for P54311 (Rattus norvegicus)
Go to UniProtKB:  P54311
Entity ID: 5
MoleculeChainsSequence LengthOrganismDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
G
71Bos taurusMutation(s): 0 
Gene Names: GNG2
Find proteins for P63212 (Bos taurus)
Go to Gene View: GNG2
Go to UniProtKB:  P63212
Entity ID: 6
MoleculeChainsSequence LengthOrganismDetails
Nanobody-35
N
126N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 1 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

Download SDF File 
Download CCD File 
R
CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Science Foundation (China)ChinaShanghai 18ZR1447800
National Natural Science Foundation of ChinaChina31300245
National Institutes of Health/National Institute of General Medical SciencesUnited StatesGM127710
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney DiseaseUnited StatesDK102495, DK111427, DK116780
National Institutes of Health/National Institute of General Medical SciencesUnited States008424

Revision History 

  • Version 1.0: 2019-04-17
    Type: Initial release
  • Version 1.1: 2019-04-24
    Type: Data collection, Database references