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MolNFT v1 · #161062 · protein

Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15

6Q2J · GROWTH/DIFFERENTIATION factor 15: “Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15”. Electron microscopy, 2 ligands (NAG, CA), 20 pockets (best druggability 0.78). MolNFT v1 #161062 on GenesisL1: 3D structure…

PDB
6Q2J
Type
protein
Length
1,738 residues
Chains
6
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
GROWTH/DIFFERENTIATION factor 15; Gdnf family receptor alpha-like; Proto-oncogene…
EC
2.7.10.1
UniProt
Q99988, Q6UXV0, P07949
Ligands
NAG, CA
Pockets
20 · best druggability 0.78

Structure

electron microscopy · 3 distinct chains · 19% helix, 33% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
A, BGROWTH/DIFFERENTIATION factor 15protein10815% helix, 48% strandQ99988
C, DGdnf family receptor alpha-likeprotein19060% helix, 1% strandQ6UXV0
E, FProto-oncogene tyrosine-protein kinase receptor ret (EC 2.7.10.1)protein5717% helix, 40% strandP07949

Ligands and binding sites

  • NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 14 copies · chains E, C, F, D
  • CA · Calcium ion · metal · 8 copies · chains E, F

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

Pockets

20 pockets found on a 1 Å grid, 13 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
13930.780.8756empty
23460.760.8649empty
34370.690.8151empty
42040.670.8523empty
52490.640.8231empty

Interfaces

9 interfaces between chains.

  • A–B · 1439 Ų buried · 6 hydrogen bonds · protein-protein
  • C–E · 1259 Ų buried · 9 hydrogen bonds · protein-protein
  • D–F · 1253 Ų buried · 9 hydrogen bonds · protein-protein
  • A–C · 592 Ų buried · 1 hydrogen bond · protein-protein
  • B–D · 588 Ų buried · 1 hydrogen bond · protein-protein

Modifications

Observed in the structure: 55 disulfide, 14 glycan (disulfide, N-glycosylation).

Compared structures

  • 6Q2J · Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15 · the same entry in another collection · chain F against F, TM-score 1.00
  • P07949 · AlphaFold monomer V2.0 prediction for proto-oncogene tyrosine-protein kinase receptor ret… · a predicted model of the same protein · chain E against A, TM-score 0.98
  • Q6UXV0 · AlphaFold monomer V2.0 prediction for gdnf family receptor alpha-like (Q6UXV0) · a predicted model of the same protein · chain C against A, TM-score 0.98
  • Q99988 · AlphaFold monomer V2.0 prediction for GROWTH/DIFFERENTIATION factor 15 (Q99988) · a predicted model of the same protein · chain B against A, TM-score 0.93

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