Cryo-EM structure of human TRPML1 with ml-SA1 and PI35P2

Structure

electron microscopy · 1 distinct chain · 53% helix, 11% strand (DSSP).

Ligands and binding sites

• HZ7 · (1R,2S,3S,4R,5S,6R)-5-{[(R)-[(2R)-2,3-bis{[(1s)-1-hydroxyoctyl]oxy}propoxy](hydroxy)phosphoryl]oxy}-2,4, 6-trihydroxycyclohexane-1,3-diyl bis[dihydrogen (phosphate)] · ligand · 4 copies · chains A, B, C, D
• AQV · 2-{2-oxo-2-[(4S)-2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl]ethyl}-1H-isoindole-1,3(2H)-dione · ligand · 4 copies · chains A, D, B, C

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

Pockets

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

Interfaces

6 interfaces between chains.

• B–C · 3669 Ų buried · 17 hydrogen bonds · protein-protein
• A–D · 3657 Ų buried · 18 hydrogen bonds · protein-protein
• C–D · 3653 Ų buried · 17 hydrogen bonds · protein-protein
• A–B · 3648 Ų buried · 18 hydrogen bonds · protein-protein
• B–D · 20 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 8 disulfide, 4 covalent (disulfide, covalent ligand).

Compared structures

• 6E7Z · cryo-EM structure of human TRPML1 with ML-SA1 and PI35P2 · the same entry in another collection · chain A against A, TM-score 1.00
• Q9GZU1 · AlphaFold monomer V2.0 prediction for mucolipin-1 (Q9GZU1) · a predicted model of the same protein · chain A against A, TM-score 0.93

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt Q9GZU1
• Elsewhere: RCSB PDB 6E7Z · PDBe 6E7Z · UniProt Q9GZU1