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Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble

Electron Microscopy
4.1Å resolution
PDB entry 5fn3 coloured by chain, front view.
PDB entry 5fn3 coloured by chain, side view.
PDB entry 5fn3 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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Assembly Name: Gamma-secretase complex, APH1A-PSEN1 variant
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Multimeric state: hetero pentamer
Accessible surface area: 56593.42 Å2
Buried surface area: 12792.26 Å2
Dissociation area: 762.48 Å2
Dissociation energy (ΔGdiss): 9.18 kcal/mol
Dissociation entropy (TΔSdiss): 8.58 kcal/mol
Symmetry number: 1
PDBe Complex ID: PDB-CPX-156018

Macromolecules

Nicastrin
Chain: A
Length: 709 amino acids
Theoretical weight: 78.48 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q92542 (Residues: 1-709; Coverage: 100%)
Gene names: KIAA0253, NCSTN, UNQ1874/PRO4317
Pfam:
InterPro:
Nicastrin in PDB entry 5fn3, assembly 1, front view.
Nicastrin in PDB entry 5fn3, assembly 1, side view.
Nicastrin in PDB entry 5fn3, assembly 1, top view.
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Presenilin-1
Chain: B
Length: 467 amino acids
Theoretical weight: 52.65 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49768 (Residues: 1-467; Coverage: 100%)
Gene names: AD3, PS1, PSEN1, PSNL1
Pfam: Presenilin
InterPro:
Presenilin-1 in PDB entry 5fn3, assembly 1, front view.
Presenilin-1 in PDB entry 5fn3, assembly 1, side view.
Presenilin-1 in PDB entry 5fn3, assembly 1, top view.
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Gamma-secretase subunit APH-1A
Chain: C
Length: 265 amino acids
Theoretical weight: 29.02 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q96BI3 (Residues: 1-265; Coverage: 100%)
Gene names: APH1A, CGI-78, PSF, UNQ579/PRO1141
Pfam: Aph-1 protein
InterPro: Gamma-secretase subunit Aph-1
Gamma-secretase subunit APH-1A in PDB entry 5fn3, assembly 1, front view.
Gamma-secretase subunit APH-1A in PDB entry 5fn3, assembly 1, side view.
Gamma-secretase subunit APH-1A in PDB entry 5fn3, assembly 1, top view.
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Gamma-secretase subunit PEN-2
Chain: D
Length: 101 amino acids
Theoretical weight: 12.04 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q9NZ42 (Residues: 1-101; Coverage: 100%)
Gene names: MDS033, PEN2, PSENEN
Pfam: Presenilin enhancer-2 subunit of gamma secretase
InterPro: Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit
Gamma-secretase subunit PEN-2 in PDB entry 5fn3, assembly 1, front view.
Gamma-secretase subunit PEN-2 in PDB entry 5fn3, assembly 1, side view.
Gamma-secretase subunit PEN-2 in PDB entry 5fn3, assembly 1, top view.
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POLY ALA CHAIN
Chain: G
Length: 24 amino acids
Theoretical weight: 1.72 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
POLY ALA CHAIN in PDB entry 5fn3, assembly 1, front view.
POLY ALA CHAIN in PDB entry 5fn3, assembly 1, side view.
POLY ALA CHAIN in PDB entry 5fn3, assembly 1, top view.
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