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Cryo-EM structure of the lysosomal folliculin complex (flcn-FNIP2- raga-ragc-ragulator)

Analyse Cryo-EM structure of the lysosomal folliculin complex (flcn-FNIP2… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
6NZD
Type
protein
Length
1,810 residues
Chains
9
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Ragulator complex protein LAMTOR1; Ragulator complex protein LAMTOR2; Ragulator complex…
UniProt
Q6IAA8, Q9Y2Q5, Q9UHA4, Q0VGL1, A0A0C4DGV4, Q7L523, Q9HB90, Q8NFG4, Q9P278
Ligands
GDP, L8S
Pockets
20 · best druggability 0.81

Structure

electron microscopy · 9 distinct chains · 43% helix, 20% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
ARagulator complex protein LAMTOR1protein8158% helix, 1% strandQ6IAA8
BRagulator complex protein LAMTOR2protein12640% helix, 28% strandQ9Y2Q5
CRagulator complex protein LAMTOR3protein12140% helix, 30% strandQ9UHA4
DRagulator complex protein LAMTOR4protein9026% helix, 40% strandQ0VGL1
EHepatitis B virus X interacting proteinprotein9131% helix, 37% strandA0A0C4DGV4
FRAS-related GTP-binding protein aprotein22743% helix, 23% strandQ7L523
GRAS-related GTP-binding protein Cprotein29941% helix, 19% strandQ9HB90
HFolliculinprotein38743% helix, 16% strandQ8NFG4
IFolliculin-interacting protein 2protein38848% helix, 12% strandQ9P278

Ligands and binding sites

  • GDP · Guanosine-5'-diphosphate · ligand · chains F, H, I
  • L8S · 9-{5-O-[(S)-hydroxy{[(r)-hydroxy(thiophosphonooxy) phosphoryl]oxy}phosphoryl]-alpha-L-arabinofuranosyl}-3,9-dihydro-1H-purine-2,6-dione · ligand · chains G

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

Pockets

20 pockets found on a 1 Å grid, 12 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
110300.810.83122empty
210450.810.82109empty
38000.780.8182empty
49600.780.8096GDP
53920.730.8442L8S

Interfaces

20 interfaces between chains.

  • H–I · 1818 Ų buried · 9 hydrogen bonds · protein-protein
  • B–C · 1336 Ų buried · 27 hydrogen bonds · protein-protein
  • F–G · 1243 Ų buried · 15 hydrogen bonds · protein-protein
  • D–E · 1052 Ų buried · 18 hydrogen bonds · protein-protein
  • A–E · 982 Ų buried · 4 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 1 disulfide (disulfide).

Compared structures

  • 6NZD · Cryo-EM Structure of the Lysosomal Folliculin Complex (FLCN-FNIP2-RagA-RagC-Ragulator) · the same entry in another collection · chain I against I, TM-score 1.00
  • Q9UHA4 · AlphaFold monomer V2.0 prediction for ragulator complex protein LAMTOR3 (Q9UHA4) · a predicted model of the same protein · chain C against A, TM-score 0.98
  • Q9HB90 · AlphaFold monomer V2.0 prediction for RAS-related GTP-binding protein C (Q9HB90) · a predicted model of the same protein · chain G against A, TM-score 0.97
  • Q9P278 · AlphaFold monomer V2.0 prediction for folliculin-interacting protein 2 (Q9P278) · a predicted model of the same protein · chain I against A, TM-score 0.96

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