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Cryo-EM structure of urocortin 1-bound corticotropin-releasing factor 1 receptor in complex with gs protein and NB35

Analyse Cryo-EM structure of urocortin 1-bound corticotropin-releasing factor 1… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
6PB0
Type
protein
Length
1,068 residues
Chains
6
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Corticotropin-releasing factor receptor 1; Urocortin; Guanine nucleotide-binding protein…
UniProt
P34998, P55089, P63092, P63096, P62873, P59768
Ligands
PLM, CLR
Pockets
14 · best druggability 0.83

Structure

electron microscopy · 6 distinct chains · 38% helix, 22% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
RCorticotropin-releasing factor receptor 1protein28178% helix, 0% strandP34998
UUrocortinprotein3979% helix, 0% strandP55089
AGuanine nucleotide-binding protein G(S) subunit alpha isoforms SHORT,GUANINE nucleotide-binding protein G(I) subunit alpha- 1,GUANINE nucleotide-binding protein G(S) subunit alpha isoforms shortprotein22742% helix, 16% strandP63092, P63096
BGuanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1protein3387% helix, 44% strandP62873
GGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2protein5751% helix, 0% strandP59768
NNanobody 35protein1265% helix, 41% strand—

Ligands and binding sites

  • PLM · Palmitic acid · ligand · 7 copies · chains R
  • CLR · Cholesterol · ligand · 5 copies · chains R

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

Pockets

14 pockets found on a 1 Å grid, 8 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
19010.830.8583empty
210080.760.7973empty
310970.760.7876empty
42720.690.8551empty
53320.640.8035empty

Interfaces

7 interfaces between chains.

  • B–G · 2220 Ų buried · 14 hydrogen bonds · protein-protein
  • R–U · 1540 Ų buried · 11 hydrogen bonds · protein-protein
  • A–B · 1528 Ų buried · 16 hydrogen bonds · protein-protein
  • R–A · 1110 Ų buried · 8 hydrogen bonds · protein-protein
  • A–N · 953 Ų buried · 14 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 3 disulfide (disulfide).

Compared structures

  • 6PB0 · Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in… · the same entry in another collection · chain N against N, TM-score 1.00
  • P62873 · 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 0.99
  • P34998 · AlphaFold monomer V2.0 prediction for corticotropin-releasing factor receptor 1 (P34998) · a predicted model of the same protein · chain R against A, TM-score 0.94
  • P59768 · 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 0.88
  • P63092 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(S) subunit… · a predicted model of the same protein · chain A against A, TM-score 0.84
  • P55089 · AlphaFold monomer V2.0 prediction for urocortin (P55089) · a predicted model of the same protein · chain U against A, TM-score 0.83
  • P63096 · AlphaFold monomer V2.0 prediction for guanine nucleotide-binding protein G(I) subunit… · a predicted model of the same protein · chain A against A, TM-score 0.74

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