8X53: Human gamma-secretase
Cryo-EM structure of human gamma-secretase in complex with Abeta46. Determined by electron microscopy at 3.0 Å resolution. Released 29 May 2024.
- Method
- Electron microscopy
- Resolution
- 3.0 Å
- Organism
- Homo sapiens
- Chains
- 5
- Atoms
- 10,947
- Mol. weight
- 189.15 kDa
- Ligands
- NAG, PC1, CLR
- Released
- 29 May 2024
Explore 8X53 in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
8X53 contains 65 α-helices and 36 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: 30 helices, 29 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 37-39 | 3 | |
| β-strand | 42-44 | 3 | 1 |
| β-strand | 47-49 | 3 | 1 |
| β-strand | 53-54 | 2 | 2 |
| β-strand | 59-60 | 2 | 2 |
| β-strand | 61 | 1 | 3 |
| β-strand | 69-76 | 8 | 1 |
| α-helix | 80-83 | 4 | |
| α-helix | 84-88 | 5 | |
| β-strand | 94-99 | 6 | 1 |
| α-helix | 105-112 | 8 | |
| β-strand | 118-124 | 7 | 1 |
| β-strand | 135 | 1 | 4 |
| α-helix | 154-156 | 3 | |
| β-strand | 168 | 1 | 4 |
| α-helix | 171-173 | 3 | |
| β-strand | 175 | 1 | 3 |
| β-strand | 180-183 | 4 | 1 |
| α-helix | 186-199 | 14 | |
| α-helix | 207-209 | 3 | |
| β-strand | 212-218 | 7 | 1 |
| α-helix | 227-240 | 14 | |
| β-strand | 248-250 | 3 | 2 |
| β-strand | 253-259 | 7 | 5 |
| β-strand | 275-281 | 7 | 5 |
| α-helix | 295-299 | 5 | |
| α-helix | 300-313 | 14 | |
| β-strand | 324-330 | 7 | 5 |
| α-helix | 338-348 | 11 | |
| α-helix | 356-358 | 3 | |
| β-strand | 359-365 | 7 | 5 |
| β-strand | 375-379 | 5 | 5 |
| α-helix | 384-386 | 3 | |
| α-helix | 388-405 | 18 | |
| β-strand | 412-414 | 3 | 5 |
| α-helix | 422-423 | 2 | |
| α-helix | 427-430 | 4 | |
| β-strand | 437-442 | 6 | 5 |
| α-helix | 473-477 | 5 | |
| α-helix | 479-481 | 3 | |
| α-helix | 482-501 | 20 | |
| α-helix | 515-526 | 12 | |
| α-helix | 540-545 | 6 | |
| α-helix | 550-552 | 3 | |
| α-helix | 562-575 | 14 | |
| β-strand | 577-579 | 3 | 6 |
| α-helix | 583-587 | 5 | |
| α-helix | 589-591 | 3 | |
| β-strand | 601 | 1 | 7 |
| β-strand | 604-605 | 2 | 6 |
| α-helix | 608-610 | 3 | |
| β-strand | 619-622 | 4 | 6 |
| β-strand | 623 | 1 | 7 |
| β-strand | 626-630 | 5 | 5 |
| α-helix | 633-636 | 4 | |
| β-strand | 649-651 | 3 | 2 |
| β-strand | 657-663 | 7 | 1 |
| α-helix | 666-692 | 27 | |
| α-helix | 694-697 | 4 | |
Chain B: 15 helices, 4 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 79-102 | 24 | |
| 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 | 8 |
| α-helix | 195-214 | 20 | |
| α-helix | 219-239 | 21 | |
| α-helix | 243-262 | 20 | |
| α-helix | 267-277 | 11 | |
| α-helix | 281-283 | 3 | |
| β-strand | 287-289 | 3 | 9 |
| β-strand | 380-382 | 3 | 9 |
| α-helix | 383-398 | 16 | |
| α-helix | 403-428 | 26 | |
| β-strand | 432-433 | 2 | 9 |
| α-helix | 439-448 | 10 | |
| α-helix | 449-453 | 5 | |
| α-helix | 454-462 | 9 | |
Chain C: 12 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 3-13 | 11 | |
| α-helix | 15-20 | 6 | |
| α-helix | 21-25 | 5 | |
| α-helix | 29-60 | 32 | |
| α-helix | 65-102 | 38 | |
| α-helix | 114-139 | 26 | |
| β-strand | 146 | 1 | 1 |
| α-helix | 156-183 | 28 | |
| α-helix | 187-202 | 16 | |
| α-helix | 203-205 | 3 | |
| α-helix | 210-212 | 3 | |
| α-helix | 215-231 | 17 | |
| α-helix | 236-240 | 5 | |
Chain D: 5 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-21 | 14 | |
| α-helix | 27-36 | 10 | |
| α-helix | 39-42 | 4 | |
| α-helix | 50-80 | 31 | |
| α-helix | 88-91 | 4 | |
| β-strand | 93-95 | 3 | 8 |
Chain E: 3 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 26-27 | 2 | |
| α-helix | 28-32 | 5 | |
| α-helix | 33-39 | 7 | |
| β-strand | 44-45 | 2 | 9 |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Nicastrin | A | protein | 709 | Homo sapiens | Q92542 (AlphaFold model) |
| Presenilin-1 | B | protein | 467 | Homo sapiens | P49768 (AlphaFold model) |
| Gamma-secretase subunit APH-1A | C | protein | 265 | Homo sapiens | Q96BI3 (AlphaFold model) |
| Gamma-secretase subunit PEN-2 | D | protein | 143 | Homo sapiens | Q9NZ42 (AlphaFold model) |
| Amyloid-beta precursor protein | E | protein | 46 | Homo sapiens | P05067 |
Sequence of entity 1 (A), FASTA
>8X53_1 Nicastrin (chains A)
MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
Sequence of entity 2 (B), FASTA
>8X53_2 Presenilin-1 (chains B)
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Sequence of entity 3 (C), FASTA
>8X53_3 Gamma-secretase subunit APH-1A (chains C)
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
Sequence of entity 4 (D), FASTA
>8X53_4 Gamma-secretase subunit PEN-2 (chains D)
MASWSHPQFEKGGGARGGSGGGSWSHPQFEKGFDYKDDDDKGTNLERVSNEEKLNLCRKY
YLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIF
QIYRPRWGALGDYLSFTIPLGTP
Sequence of entity 5 (E), FASTA
>8X53_5 Amyloid-beta precursor protein (chains E)
DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIV
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| NAG | 2-acetamido-2-deoxy-beta-D-glucopyranose | C8 H15 N O6 | 6 |
| PC1 | 1,2-diacyl-sn-glycero-3-phosphocholine | C44 H88 N O8 P | 3 |
| CLR | Cholesterol | C27 H46 O | 2 |
Primary citation
Molecular mechanism of substrate recognition and cleavage by human gamma-secretase. Guo, X., Li, H., Yan, C. et al. Science (2024) 384:1091-1095. DOI 10.1126/science.adn5820 · 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
Browse structure collections
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