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Cryo-EM structure of gamma secretase in complex with a Notch fragment

Electron Microscopy
2.7Å resolution
PDB entry 6idf coloured by chain, front view.
PDB entry 6idf coloured by chain, side view.
PDB entry 6idf 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 and Neurogenic locus notch homolog protein 1
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Multimeric state: hetero pentamer
Accessible surface area: 62151.64 Å2
Buried surface area: 26970.29 Å2
Dissociation area: 2,117.12 Å2
Dissociation energy (ΔGdiss): 37.09 kcal/mol
Dissociation entropy (TΔSdiss): 11.24 kcal/mol
Symmetry number: 1
PDBe Complex ID: PDB-CPX-155481

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 6idf, assembly 1, front view.
Nicastrin in PDB entry 6idf, assembly 1, side view.
Nicastrin in PDB entry 6idf, assembly 1, top view.
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Presenilin-1
Chain: B
Length: 467 amino acids
Theoretical weight: 52.64 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 6idf, assembly 1, front view.
Presenilin-1 in PDB entry 6idf, assembly 1, side view.
Presenilin-1 in PDB entry 6idf, 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 6idf, assembly 1, front view.
Gamma-secretase subunit APH-1A in PDB entry 6idf, assembly 1, side view.
Gamma-secretase subunit APH-1A in PDB entry 6idf, 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 6idf, assembly 1, front view.
Gamma-secretase subunit PEN-2 in PDB entry 6idf, assembly 1, side view.
Gamma-secretase subunit PEN-2 in PDB entry 6idf, assembly 1, top view.
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Notch 1 intracellular domain
Chain: E
Length: 129 amino acids
Theoretical weight: 14.76 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P46531 (Residues: 1721-1820, 1821-1847; Coverage: 5%)
Gene names: NOTCH1, TAN1
Notch 1 intracellular domain in PDB entry 6idf, assembly 1, front view.
Notch 1 intracellular domain in PDB entry 6idf, assembly 1, side view.
Notch 1 intracellular domain in PDB entry 6idf, assembly 1, top view.
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