Cryo-EM structure of human full-length extrasynaptic BETA3DELTA GABA(A)R in complex with thip (gaboxadol), histamine and nanobody NB25

Structure

electron microscopy · 3 distinct chains · 32% helix, 34% strand (DSSP).

Ligands and binding sites

• HSM · Histamine · ligand · 3 copies · chains A, B, C, D
• EI7 · 4,5,6,7-tetrahydro-[1,2]oxazolo[5,4-c]pyridin-3-one · ligand · chains D, E
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 17 copies · chains A, B, K, C, L, D, M, E
• MAN · alpha-D-mannopyranose · sugar · 8 copies · chains A, B, K, C, L, D, M
• BMA · beta-D-mannopyranose · sugar · 4 copies · chains A, B, C, D

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

Pockets

20 pockets found on a 1 Å grid, 16 with a druggability of 0.5 or more.

Interfaces

11 interfaces between chains.

• A–B · 2752 Ų buried · 20 hydrogen bonds · protein-protein
• C–D · 2732 Ų buried · 19 hydrogen bonds · protein-protein
• B–C · 2710 Ų buried · 20 hydrogen bonds · protein-protein
• D–E · 2705 Ų buried · 20 hydrogen bonds · protein-protein
• A–E · 2471 Ų buried · 14 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 9 glycan, 8 disulfide (N-glycosylation, disulfide).

Compared structures

• 7QND · Cryo-EM structure of human full-length extrasynaptic beta3delta GABA(A)R in complex with… · the same entry in another collection · chain M against M, TM-score 1.00
• P28472 · AlphaFold monomer V2.0 prediction for gamma-aminobutyric acid receptor subunit beta-3… · a predicted model of the same protein · chain B against A, TM-score 0.99

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 P28472
• Every structure of UniProt O14764
• Elsewhere: RCSB PDB 7QND · PDBe 7QND · UniProt P28472 · UniProt O14764