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Cryo-EM structure of mammalian endolysosomal TRPML1 channel in nanodiscs in closed I conformation at 3.64 ångström resolution

Analyse Cryo-EM structure of mammalian endolysosomal TRPML1 channel in nanodiscs in… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
5WPQ
Type
protein
Length
1,816 residues
Chains
4
Method
electron microscopy
Collection
MolNFT v1 / PDB
Contract
0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner
0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule
Mucolipin-1
UniProt
Q99J21
Ligands
NAG, NA
Pockets
20 · best druggability 0.84

Structure

electron microscopy · 1 distinct chain · 57% helix, 13% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
A, B, C, DMucolipin-1protein45457% helix, 13% strandQ99J21

Ligands and binding sites

  • NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 8 copies · chains A, B, C, D
  • NA · Sodium ion · metal

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

Pockets

20 pockets found on a 1 Å grid, 18 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
17750.840.8687empty
28570.730.7758empty
37070.720.7862empty
46450.710.7948empty
56380.710.7849empty

Interfaces

6 interfaces between chains.

  • C–D · 3561 Ų buried · 19 hydrogen bonds · protein-protein
  • B–C · 3556 Ų buried · 19 hydrogen bonds · protein-protein
  • A–B · 3549 Ų buried · 19 hydrogen bonds · protein-protein
  • A–D · 3543 Ų buried · 19 hydrogen bonds · protein-protein
  • A–C · 17 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 glycan (N-glycosylation).

Compared structures

  • 5WPQ · Cryo-EM structure of mammalian endolysosomal TRPML1 channel in nanodiscs in closed I… · the same entry in another collection · chain A against A, TM-score 1.00
  • Q99J21 · AlphaFold monomer V2.0 prediction for mucolipin-1 (Q99J21) · a predicted model of the same protein · chain A against A, TM-score 0.96

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