8OQZ: Nicastrin
Structure of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc in complex with Ab46. Determined by electron microscopy at 3.4 Å resolution. Released 24 Apr 2024.
- Method
- Electron microscopy
- Resolution
- 3.4 Å
- Organism
- Homo sapiens
- Chains
- 5
- Atoms
- 11,129
- Mol. weight
- 192.3 kDa
- Ligands
- NAG, PC1
- Released
- 24 Apr 2024
Explore 8OQZ in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
8OQZ contains 66 α-helices and 38 β-strands across 5 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.
Chain A: 33 helices, 33 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 35-39 | 5 | |
| β-strand | 42-43 | 2 | 1 |
| β-strand | 47-48 | 2 | 2 |
| α-helix | 49-50 | 2 | |
| β-strand | 53-54 | 2 | 3 |
| β-strand | 59-60 | 2 | 3 |
| β-strand | 61-62 | 2 | 4 |
| α-helix | 64-65 | 2 | |
| β-strand | 69-72 | 4 | 1 |
| β-strand | 74-76 | 3 | 2 |
| α-helix | 79-83 | 5 | |
| α-helix | 84-88 | 5 | |
| β-strand | 95-99 | 5 | 2 |
| α-helix | 100-102 | 3 | |
| α-helix | 105-113 | 9 | |
| α-helix | 115-117 | 3 | |
| β-strand | 120-124 | 5 | 2 |
| α-helix | 129-130 | 2 | |
| β-strand | 135 | 1 | 5 |
| β-strand | 149 | 1 | 6 |
| β-strand | 152 | 1 | 6 |
| α-helix | 154-156 | 3 | |
| β-strand | 168 | 1 | 5 |
| α-helix | 171-173 | 3 | |
| β-strand | 175-176 | 2 | 4 |
| β-strand | 180-183 | 4 | 2 |
| α-helix | 186-198 | 13 | |
| α-helix | 203-205 | 3 | |
| β-strand | 213-218 | 6 | 1 |
| α-helix | 227-239 | 13 | |
| β-strand | 248-250 | 3 | 3 |
| β-strand | 253-259 | 7 | 7 |
| β-strand | 275-280 | 6 | 7 |
| α-helix | 295-299 | 5 | |
| α-helix | 300-313 | 14 | |
| β-strand | 324-329 | 6 | 7 |
| α-helix | 338-349 | 12 | |
| α-helix | 356-358 | 3 | |
| β-strand | 359-365 | 7 | 7 |
| β-strand | 375 | 1 | 8 |
| β-strand | 377-379 | 3 | 7 |
| α-helix | 383-386 | 4 | |
| α-helix | 388-405 | 18 | |
| β-strand | 412 | 1 | 8 |
| α-helix | 421-423 | 3 | |
| α-helix | 427-433 | 7 | |
| β-strand | 438-442 | 5 | 7 |
| α-helix | 473-476 | 4 | |
| α-helix | 479-481 | 3 | |
| α-helix | 482-502 | 21 | |
| α-helix | 515-526 | 12 | |
| α-helix | 532-535 | 4 | |
| α-helix | 541-545 | 5 | |
| α-helix | 550-552 | 3 | |
| α-helix | 562-575 | 14 | |
| β-strand | 577-579 | 3 | 9 |
| α-helix | 583-587 | 5 | |
| β-strand | 601-605 | 5 | 9 |
| β-strand | 609 | 1 | 10 |
| β-strand | 616 | 1 | 10 |
| β-strand | 619-623 | 5 | 9 |
| β-strand | 626-630 | 5 | 7 |
| β-strand | 649-651 | 3 | 3 |
| β-strand | 657-662 | 6 | 1 |
| α-helix | 666-692 | 27 | |
| α-helix | 694-697 | 4 | |
Chain B: 14 helices, 3 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 74-102 | 29 | |
| α-helix | 125-155 | 31 | |
| α-helix | 159-171 | 13 | |
| α-helix | 172-177 | 6 | |
| α-helix | 178-189 | 12 | |
| β-strand | 193-194 | 2 | 11 |
| α-helix | 195-214 | 20 | |
| α-helix | 219-239 | 21 | |
| α-helix | 243-262 | 20 | |
| α-helix | 267-277 | 11 | |
| β-strand | 287 | 1 | 12 |
| β-strand | 382 | 1 | 12 |
| α-helix | 383-398 | 16 | |
| α-helix | 404-428 | 25 | |
| α-helix | 435-448 | 14 | |
| α-helix | 449-453 | 5 | |
| α-helix | 454-462 | 9 | |
Chain C: 10 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 3-20 | 18 | |
| α-helix | 21-25 | 5 | |
| α-helix | 30-59 | 30 | |
| α-helix | 65-104 | 40 | |
| α-helix | 109-112 | 4 | |
| α-helix | 113-139 | 27 | |
| β-strand | 145 | 1 | 1 |
| α-helix | 155-182 | 28 | |
| α-helix | 186-205 | 20 | |
| α-helix | 209-230 | 22 | |
| α-helix | 235-240 | 6 | |
Chain D: 7 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-20 | 13 | |
| α-helix | 21-23 | 3 | |
| α-helix | 27-36 | 10 | |
| α-helix | 39-42 | 4 | |
| α-helix | 50-81 | 32 | |
| α-helix | 87-92 | 6 | |
| β-strand | 93-95 | 3 | 11 |
| α-helix | 96-97 | 2 | |
Chain E: 2 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 27-36 | 10 | |
| α-helix | 37-41 | 5 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Nicastrin | A | protein | 717 | Homo sapiens | Q92542 (AlphaFold model) |
| Presenilin-1 CTF12 | B | protein | 467 | Homo sapiens | P49768 (AlphaFold model) |
| Gamma-secretase subunit APH-1B | C | protein | 257 | Homo sapiens | Q8WW43 (AlphaFold model) |
| Gamma-secretase subunit PEN-2 | D | protein | 101 | Homo sapiens | Q9NZ42 (AlphaFold model) |
| Amyloid-beta peptide 1-46 | E | protein | 66 | Homo sapiens | |
Sequence of entity 1 (A), FASTA
>8OQZ_1 Nicastrin (chains A)
MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSYGTLEVLFQ
Sequence of entity 2 (B), FASTA
>8OQZ_2 Presenilin-1 CTF12 (chains B)
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYALVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Sequence of entity 3 (C), FASTA
>8OQZ_3 Gamma-secretase subunit APH-1B (chains C)
MTAAVFFGCAFIAFGPALALYVFTIATEPLRIIFLIAGAFFWLVSLLISSLVWFMARVII
DNKDGPTQKYLLIFGAFVSVYIQEMFRFAYYKLLKKASEGLKSINPGETAPSMRLLAYVS
GLGFGIMSGVFSFVNTLSDSLGPGTVGIHGDSPQFFLYSAFMTLVIILLHVFWGIVFFDG
CEKKKWGILLIVLLTHLLVSAQTFISSYYGINLASAFIILVLMGTWAFLAAGGSCRSLKL
CLLCQDKNFLLYNQRSR
Sequence of entity 4 (D), FASTA
>8OQZ_4 Gamma-secretase subunit PEN-2 (chains D)
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRS
AVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
Sequence of entity 5 (E), FASTA
>8OQZ_5 Amyloid-beta peptide 1-46 (chains E)
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXX
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| NAG | 2-acetamido-2-deoxy-beta-D-glucopyranose | C8 H15 N O6 | 8 |
| PC1 | 1,2-diacyl-sn-glycero-3-phosphocholine | C44 H88 N O8 P | 14 |
Primary citation
Apo and A beta 46-bound gamma-secretase structures provide insights into amyloid-beta processing by the APH-1B isoform. Odorcic, I., Hamed, M.B., Lismont, S. et al. Nat Commun (2024) 15:4479-4479. DOI 10.1038/s41467-024-48776-2 · PubMed
Other PDB entries of the same protein (UniProt Q92542 (AlphaFold model), which also has an AlphaFold model), best resolution first:
- 8KCS 2.4 Å, Cryo-EM structure of human gamma-secretase in complex with BMS906024
- 6IYC 2.6 Å, Recognition of the Amyloid Precursor Protein by Human gamma-secretase
- 7D8X 2.6 Å, CryoEM structure of human gamma-secretase in complex with E2012 and L685458
- 8K8E 2.6 Å, Human gamma-secretase in complex with a substrate mimetic
- 8KCT 2.6 Å, Cryo-EM structure of human gamma-secretase in complex with Nirogacestat
- 6IDF 2.7 Å, Cryo-EM structure of gamma secretase in complex with a Notch fragment
- 8KCU 2.7 Å, Cryo-EM structure of human gamma-secretase in complex with MK-0752
- 8KCO 2.8 Å, Cryo-EM structure of human gamma-secretase in complex with RO4929097
- 7Y5T 2.9 Å, CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560
- 8X52 2.9 Å, Cryo-EM structure of human gamma-secretase in complex with Abeta49
- 8X54 2.9 Å, Cryo-EM structure of human gamma-secretase in complex with APP-C99
- 9K95 2.9 Å, Cryo-EM structure of human gamma-secretase in complex with compound E
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