Research workbench

Recognition of the amyloid precursor protein by human gamma-secretase

Analyse Recognition of the amyloid precursor protein by human gamma-secretase in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB: 6IYC
Type: protein
Length: 1,355 residues
Chains: 5
Method: electron microscopy
Collection: MolNFT v1 / PDB
Contract: 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner: 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule: Nicastrin; Presenilin-1; Gamma-secretase subunit aph-1A; Gamma-secretase subunit pen-2…
EC: 3.4.23.-
UniProt: Q92542, P49768, Q96BI3, Q9NZ42, P05067
Ligands: CLR, PC1, NAG, BMA
Pockets: 18 · best druggability 0.74

Structure

electron microscopy · 5 distinct chains · 53% helix, 11% strand (DSSP).

Chain	Molecule	Type	Residues	Secondary structure	UniProt
A	Nicastrin	protein	667	33% helix, 18% strand	Q92542
B	Presenilin-1 (EC 3.4.23.-)	protein	311	73% helix, 4% strand	P49768
C	Gamma-secretase subunit aph-1A	protein	243	76% helix, 0% strand	Q96BI3
D	Gamma-secretase subunit pen-2	protein	100	69% helix, 3% strand	Q9NZ42
E	Amyloid-beta A4 protein	protein	34	41% helix, 18% strand	P05067

Ligands and binding sites

CLR · Cholesterol · ligand · 3 copies · chains C
PC1 · 1,2-diacyl-sn-glycero-3-phosphocholine · ligand · 2 copies · chains B, C, A
NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 18 copies · chains A, C
BMA · beta-D-mannopyranose · sugar · 3 copies · chains A

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

Pockets

18 pockets found on a 1 Å grid, 9 with a druggability of 0.5 or more.

Pocket	Volume (Å³)	Druggability	Buriedness	Lining residues	Inside
1	92	0.74	0.96	28	empty
2	697	0.74	0.80	63	empty
3	612	0.71	0.79	46	PC1
4	526	0.70	0.79	47	empty
5	598	0.67	0.76	39	PC1

Interfaces

7 interfaces between chains.

B–C · 1854 Å² buried · 11 hydrogen bonds · protein-protein
A–C · 1762 Å² buried · 8 hydrogen bonds · protein-protein
B–E · 1579 Å² buried · 12 hydrogen bonds · protein-protein
B–D · 1186 Å² buried · 8 hydrogen bonds · protein-protein
A–D · 504 Å² buried · 4 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 12 glycan, 4 disulfide, 2 covalent (N-glycosylation, disulfide, covalent ligand).

Compared structures

6IYC · Recognition of the Amyloid Precursor Protein by Human gamma-secretase · the same entry in another collection · chain E against E, TM-score 1.00
Q92542 · AlphaFold monomer V2.0 prediction for nicastrin (Q92542) · a predicted model of the same protein · chain A against A, TM-score 0.98
P49768 · AlphaFold monomer V2.0 prediction for presenilin-1 (P49768) · a predicted model of the same protein · chain B against A, TM-score 0.97
Q96BI3 · AlphaFold monomer V2.0 prediction for gamma-secretase subunit aph-1A (Q96BI3) · a predicted model of the same protein · chain C against A, TM-score 0.97
Q9NZ42 · AlphaFold monomer V2.0 prediction for gamma-secretase subunit pen-2 (Q9NZ42) · a predicted model of the same protein · chain D against A, TM-score 0.96
P05067 · AlphaFold monomer V2.0 prediction for amyloid-beta precursor protein (P05067) · a predicted model of the same protein · chain E against A, TM-score 0.51

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 Q92542
Every structure of UniProt P49768
Every structure of UniProt Q96BI3
Every structure of UniProt Q9NZ42
Every structure of UniProt P05067
Elsewhere: RCSB PDB 6IYC · PDBe 6IYC · UniProt Q92542 · UniProt P49768 · UniProt Q96BI3 · UniProt Q9NZ42 · UniProt P05067

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