CryoEM structure of human gamma-secretase in complex with E2012 and L685458. Determined by electron microscopy at 2.6 Å resolution. Released 27 Jan 2021.
Explore 7D8X in 3D Show helices and sheets RCSB PDB PDBe
7D8X contains 65 α-helices and 36 β-strands across 4 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.
| Element | Residues | Length | Sheet |
|---|---|---|---|
| β-strand | 42-43 | 2 | 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 | |
| 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 | 201-202 | 2 | |
| α-helix | 207-209 | 3 | |
| β-strand | 212-218 | 7 | 1 |
| β-strand | 221 | 1 | 5 |
| α-helix | 227-240 | 14 | |
| β-strand | 248-250 | 3 | 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 | |
| α-helix | 356-358 | 3 | |
| β-strand | 359-365 | 7 | 6 |
| β-strand | 375-379 | 5 | 6 |
| α-helix | 384-386 | 3 | |
| α-helix | 388-405 | 18 | |
| β-strand | 412-414 | 3 | 6 |
| α-helix | 422-423 | 2 | |
| α-helix | 427-430 | 4 | |
| β-strand | 438-442 | 5 | 6 |
| α-helix | 482-501 | 20 | |
| α-helix | 508-510 | 3 | |
| 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 | 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 | 633-636 | 4 | |
| β-strand | 649-651 | 3 | 2 |
| α-helix | 652 | 1 | |
| β-strand | 653 | 1 | 5 |
| β-strand | 657-663 | 7 | 1 |
| α-helix | 666-692 | 27 | |
| α-helix | 694-697 | 4 |
| Element | Residues | Length | Sheet |
|---|---|---|---|
| α-helix | 83-102 | 20 | |
| α-helix | 125-155 | 31 | |
| α-helix | 159-171 | 13 | |
| α-helix | 172-177 | 6 | |
| α-helix | 178-188 | 11 | |
| β-strand | 193-194 | 2 | 9 |
| α-helix | 195-214 | 20 | |
| α-helix | 219-239 | 21 | |
| α-helix | 243-262 | 20 | |
| α-helix | 267-277 | 11 | |
| β-strand | 287-289 | 3 | 10 |
| β-strand | 380-382 | 3 | 10 |
| α-helix | 383-398 | 16 | |
| α-helix | 405-428 | 24 | |
| α-helix | 435-451 | 17 | |
| α-helix | 453-463 | 11 |
| Element | Residues | Length | Sheet |
|---|---|---|---|
| α-helix | 3-13 | 11 | |
| α-helix | 15-20 | 6 | |
| α-helix | 21-25 | 5 | |
| α-helix | 29-59 | 31 | |
| α-helix | 67-99 | 33 | |
| α-helix | 100-104 | 5 | |
| 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 |
| 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 | 88-91 | 4 | |
| β-strand | 93-95 | 3 | 9 |
| 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) |
>7D8X_1 Nicastrin (chains A) MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
>7D8X_2 Presenilin-1 (chains B) MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
>7D8X_3 Gamma-secretase subunit APH-1A (chains C) MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ RSLLCRRQEDSRVMVYSALRIPPED
>7D8X_4 Gamma-secretase subunit PEN-2 (chains D) MASWSHPQFEKGGGARGGSGGGSWSHPQFEKGFDYKDDDDKGTNLERVSNEEKLNLCRKY YLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIF QIYRPRWGALGDYLSFTIPLGTP
| ID | Name | Formula | Copies |
|---|---|---|---|
| GZR | 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]… | C25 H26 F N3 O2 | 1 |
| PC1 | 1,2-diacyl-sn-glycero-3-phosphocholine | C44 H88 N O8 P | 2 |
| NAG | 2-acetamido-2-deoxy-beta-D-glucopyranose | C8 H15 N O6 | 6 |
| CLR | Cholesterol | C27 H46 O | 3 |
| FTO | ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxid… | C39 H52 N4 O6 | 1 |
| PTY | Phosphatidylethanolamine | C40 H80 N O8 P | 1 |
Structural basis of gamma-secretase inhibition and modulation by small molecule drugs. Yang, G., Zhou, R., Guo, X. et al. Cell (2021) 184:521-533.e14. DOI 10.1016/j.cell.2020.11.049 · PubMed
Other PDB entries of the same protein (UniProt Q92542 (AlphaFold model), which also has an AlphaFold model), best resolution first:
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