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The cryoEM structure of human gamma-Secretase complex

Electron Microscopy
4.4Å resolution
PDB entry 4uis coloured by chain, front view.
PDB entry 4uis coloured by chain, side view.
PDB entry 4uis coloured by chain, top view.
Source organism: Homo sapiens
Assembly composition:
hetero pentamer (preferred)
Entry contents: 5 distinct polypeptide molecules

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Assemblies

Assembly 1 (preferred)
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Multimeric state: hetero pentamer
Accessible surface area: 52908.48 Å2
Buried surface area: 37.63 Å2
Dissociation area: 18.81 Å2
Dissociation energy (ΔGdiss): -25.3 kcal/mol
Dissociation entropy (TΔSdiss): 25.54 kcal/mol
Symmetry number: 1
PDBe Complex ID: PDB-CPX-112954

Macromolecules

Nicastrin
Chain: A
Length: 588 amino acids
Theoretical weight: 63.33 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q92542 (Residues: 42-665; Coverage: 84%)
Gene names: KIAA0253, NCSTN, UNQ1874/PRO4317
Pfam:
InterPro:
Nicastrin in PDB entry 4uis, assembly 1, front view.
Nicastrin in PDB entry 4uis, assembly 1, side view.
Nicastrin in PDB entry 4uis, assembly 1, top view.
PDBe-KB: UniProt Coverage View: Q92542  
158850100150200250300350400450500550
 
200400
UniProt
Q92542
Chains
Domains
Secondary structure
Flexibility predictions
Early folding residue predictions
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Presenilin-1 CTF12
Chain: B
Length: 241 amino acids
Theoretical weight: 23.55 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49768 (Residues: 404-463; Coverage: 13%)
  • Best match: P49768-4 (Residues: 81-100)
Gene names: AD3, PS1, PSEN1, PSNL1
InterPro:
Presenilin-1 CTF12 in PDB entry 4uis, assembly 1, front view.
Presenilin-1 CTF12 in PDB entry 4uis, assembly 1, side view.
Presenilin-1 CTF12 in PDB entry 4uis, assembly 1, top view.
PDBe-KB: UniProt Coverage View: P49768  
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GAMMA-SECRETASE
Chain: C
Length: 196 amino acids
Theoretical weight: 16.7 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, front view.
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, side view.
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, top view.
119620406080100120140160180
 
50100150
Chains
Chain C (auth C)
Secondary structure
Flexibility predictions
Early folding residue predictions
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GAMMA-SECRETASE
Chain: D
Length: 62 amino acids
Theoretical weight: 5.29 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, front view.
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, side view.
GAMMA-SECRETASE in PDB entry 4uis, assembly 1, top view.
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Endolysin
Chain: G
Length: 162 amino acids
Theoretical weight: 18.44 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: D9IEF7 (Residues: 1-162; Coverage: 99%)
Gene names: T4Tp126, e
Pfam: Phage lysozyme
InterPro:
Endolysin in PDB entry 4uis, assembly 1, front view.
Endolysin in PDB entry 4uis, assembly 1, side view.
Endolysin in PDB entry 4uis, assembly 1, top view.
PDBe-KB: UniProt Coverage View: D9IEF7  
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