6IDF: Gamma secretase
Cryo-EM structure of gamma secretase in complex with a Notch fragment. Determined by electron microscopy at 2.7 Å resolution. Released 26 Dec 2018.
- Method
- Electron microscopy
- Resolution
- 2.7 Å
- Organism
- Homo sapiens
- Chains
- 5
- Atoms
- 11,188
- Mol. weight
- 195.62 kDa
- Ligands
- NAG, PC1, CLR
- Released
- 26 Dec 2018
Explore 6IDF in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
6IDF 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: 29 helices, 31 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 |
| α-helix | 64-65 | 2 | |
| β-strand | 69-76 | 8 | 1 |
| α-helix | 81-83 | 3 | |
| α-helix | 84-88 | 5 | |
| β-strand | 94-99 | 6 | 1 |
| α-helix | 105-113 | 9 | |
| β-strand | 118-124 | 7 | 1 |
| β-strand | 135 | 1 | 4 |
| α-helix | 143-145 | 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 |
| β-strand | 221-222 | 2 | 5 |
| α-helix | 227-236 | 10 | |
| β-strand | 250 | 1 | 2 |
| β-strand | 253-259 | 7 | 6 |
| α-helix | 268-270 | 3 | |
| β-strand | 275-281 | 7 | 6 |
| α-helix | 295-299 | 5 | |
| α-helix | 300-313 | 14 | |
| β-strand | 324-330 | 7 | 6 |
| α-helix | 338-349 | 12 | |
| β-strand | 359-365 | 7 | 6 |
| β-strand | 375-379 | 5 | 6 |
| α-helix | 384-386 | 3 | |
| α-helix | 388-404 | 17 | |
| β-strand | 412-414 | 3 | 6 |
| α-helix | 427-430 | 4 | |
| β-strand | 438-442 | 5 | 6 |
| α-helix | 484-502 | 19 | |
| α-helix | 515-526 | 12 | |
| α-helix | 534-536 | 3 | |
| α-helix | 540-545 | 6 | |
| α-helix | 550-552 | 3 | |
| α-helix | 562-575 | 14 | |
| β-strand | 577-579 | 3 | 7 |
| α-helix | 583-587 | 5 | |
| β-strand | 601-605 | 5 | 7 |
| α-helix | 608 | 1 | |
| β-strand | 609 | 1 | 8 |
| α-helix | 610 | 1 | |
| β-strand | 616 | 1 | 8 |
| β-strand | 619-623 | 5 | 7 |
| β-strand | 626-630 | 5 | 6 |
| α-helix | 633-635 | 3 | |
| β-strand | 649-650 | 2 | 2 |
| β-strand | 652-653 | 2 | 5 |
| β-strand | 657-663 | 7 | 1 |
| α-helix | 666-692 | 27 | |
| α-helix | 694-697 | 4 | |
Chain B: 14 helices, 4 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 75-102 | 28 | |
| α-helix | 125-153 | 29 | |
| α-helix | 159-165 | 7 | |
| α-helix | 168-174 | 7 | |
| α-helix | 177-188 | 12 | |
| β-strand | 193-194 | 2 | 9 |
| α-helix | 195-213 | 19 | |
| α-helix | 219-239 | 21 | |
| α-helix | 243-262 | 20 | |
| α-helix | 267-277 | 11 | |
| β-strand | 287-289 | 3 | 10 |
| β-strand | 377-382 | 6 | 10 |
| α-helix | 383-398 | 16 | |
| α-helix | 405-428 | 24 | |
| β-strand | 432-433 | 2 | 10 |
| α-helix | 435-448 | 14 | |
| α-helix | 449-453 | 5 | |
| α-helix | 454-463 | 10 | |
Chain C: 13 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 4-13 | 10 | |
| α-helix | 16-20 | 5 | |
| α-helix | 21-25 | 5 | |
| α-helix | 29-59 | 31 | |
| α-helix | 68-106 | 39 | |
| α-helix | 114-138 | 25 | |
| α-helix | 139-141 | 3 | |
| β-strand | 146 | 1 | 1 |
| α-helix | 156-184 | 29 | |
| α-helix | 189-202 | 14 | |
| α-helix | 204-206 | 3 | |
| α-helix | 210-212 | 3 | |
| α-helix | 215-231 | 17 | |
| α-helix | 236-242 | 7 | |
Chain D: 6 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-20 | 13 | |
| α-helix | 21-23 | 3 | |
| α-helix | 27-41 | 15 | |
| α-helix | 53-58 | 6 | |
| α-helix | 60-80 | 21 | |
| α-helix | 88-91 | 4 | |
| β-strand | 93-95 | 3 | 9 |
Chain E: 4 helices, 1 β-strand
| Element | Residues | Length | Sheet |
|---|
| α-helix | 4-7 | 4 | |
| α-helix | 11-13 | 3 | |
| α-helix | 17-22 | 6 | |
| α-helix | 24-27 | 4 | |
| β-strand | 36-41 | 6 | 10 |
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 | 101 | Homo sapiens | Q9NZ42 (AlphaFold model) |
| Notch1 | E | protein | 129 | Homo sapiens | P46531 |
Sequence of entity 1 (A), FASTA
>6IDF_1 Nicastrin (chains A)
MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
Sequence of entity 2 (B), FASTA
>6IDF_2 Presenilin-1 (chains B)
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGCLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGAFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Sequence of entity 3 (C), FASTA
>6IDF_3 Gamma-secretase subunit APH-1A (chains C)
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
Sequence of entity 4 (D), FASTA
>6IDF_4 Gamma-secretase subunit PEN-2 (chains D)
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRS
AVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
Sequence of entity 5 (E), FASTA
>6IDF_5 Notch1 (chains E)
MVQSETVECPPPAQLHFMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEAS
KKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETEQKLISEEDLLESDEVDAI
EHHHHHHHH
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 | 4 |
| CLR | Cholesterol | C27 H46 O | 3 |
Primary citation
Structural basis of Notch recognition by human gamma-secretase. Yang, G., Zhou, R., Zhou, Q. et al. Nature (2019) 565:192-197. DOI 10.1038/s41586-018-0813-8 · 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
- 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
- 6LR4 3.0 Å, Molecular basis for inhibition of human gamma-secretase by small molecule
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