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

Analyse Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
6NBF
Type
protein
Length
1,148 residues
Chains
6
Method
electron microscopy
Collection
MolNFT v2 / PDB Bank
Contract
0xd58B01f6C18086e5202cdC5D7Ad3E41790360102
Owner
0xF4e1AA6f26B7DA48EeAD9B24a97927303eeA07b8
Resolution
3.0
Source
Bos taurus; Homo sapiens; Rattus norvegicus; synthetic construct; SYNTHETIC…
Molecule
Parathyroid hormone/parathyroid hormone-related peptide receptor; Long-acting parathyroid…
UniProt
Q03431, P54311, P63212
Ligands
CLR, PLM
Pockets
17 · best druggability 0.84

Structure

electron microscopy · resolution 3.0 · 6 distinct chains · 37% helix, 24% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
RParathyroid hormone/parathyroid hormone-related peptide receptorprotein36861% helix, 6% strandQ03431
PLong-acting parathyroid hormone analogprotein3291% helix, 0% strand—
AGs protein alpha subunitprotein22747% helix, 18% strand—
BGuanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1protein3386% helix, 46% strandP54311
GGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2protein5754% helix, 0% strandP63212
NNanobody-35protein1267% helix, 45% strand—

Ligands and binding sites

  • CLR · Cholesterol · ligand · 6 copies · chains R
  • PLM · Palmitic acid · ligand · 4 copies · chains R

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

17 pockets found on a 1 Å grid, 6 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
19020.840.8679empty
29850.750.7871empty
36570.750.8185empty
48930.730.7862empty
5630.720.9718empty

Interfaces

7 interfaces between chains.

  • R–P · 2162 Ų buried · 12 hydrogen bonds · protein-protein
  • B–G · 2138 Ų buried · 8 hydrogen bonds · protein-protein
  • A–B · 1545 Ų buried · 16 hydrogen bonds · protein-protein
  • A–N · 1025 Ų buried · 7 hydrogen bonds · protein-protein
  • R–A · 1005 Ų buried · 4 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 6 disulfide (disulfide).

Compared structures

  • 6NBF · Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting… · the same entry in another collection · chain R against R, TM-score 1.00
  • P54311 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I)/G(S)/G(T)… · a predicted model of the same protein · chain B against A, TM-score 1.00
  • Q03431 · AlphaFold monomer V2.0 prediction for parathyroid HORMONE/PARATHYROID hormone-related… · a predicted model of the same protein · chain R against A, TM-score 0.96
  • P63212 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I)/G(S)/G(O)… · a predicted model of the same protein · chain G against A, TM-score 0.67

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