CryoEM structure of PS2-containing gamma-secretase treated with MRK-560. Determined by electron microscopy at 3.0 Å resolution. Released 2 Nov 2022.
Explore 7Y5X in 3D Show helices and sheets RCSB PDB PDBe
7Y5X contains 54 α-helices and 32 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 |
|---|---|---|---|
| α-helix | 37-39 | 3 | |
| β-strand | 42-44 | 3 | 1 |
| β-strand | 47-48 | 2 | 1 |
| β-strand | 53-54 | 2 | 2 |
| β-strand | 59 | 1 | 2 |
| β-strand | 61 | 1 | 3 |
| β-strand | 69-75 | 7 | 1 |
| α-helix | 81-86 | 6 | |
| β-strand | 94-99 | 6 | 1 |
| α-helix | 105-113 | 9 | |
| 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 | 181-183 | 3 | 1 |
| α-helix | 186-199 | 14 | |
| α-helix | 207-209 | 3 | |
| β-strand | 212-221 | 10 | 1 |
| α-helix | 227-236 | 10 | |
| 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 | |
| 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 | 427-430 | 4 | |
| β-strand | 437-442 | 6 | 5 |
| α-helix | 476-478 | 3 | |
| α-helix | 482-501 | 20 | |
| α-helix | 515-526 | 12 | |
| α-helix | 543-545 | 3 | |
| 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 | 601-605 | 5 | 6 |
| α-helix | 608 | 1 | |
| β-strand | 609-610 | 2 | 7 |
| β-strand | 615-616 | 2 | 7 |
| β-strand | 619-623 | 5 | 6 |
| β-strand | 626-630 | 5 | 5 |
| α-helix | 633-636 | 4 | |
| β-strand | 649-651 | 3 | 2 |
| β-strand | 653-663 | 11 | 1 |
| α-helix | 666-692 | 27 | |
| α-helix | 694-697 | 4 |
| Element | Residues | Length | Sheet |
|---|---|---|---|
| α-helix | 86-106 | 21 | |
| α-helix | 174-180 | 7 | |
| α-helix | 184-195 | 12 | |
| β-strand | 199-200 | 2 | 8 |
| α-helix | 201-219 | 19 | |
| α-helix | 225-245 | 21 | |
| α-helix | 252-261 | 10 | |
| α-helix | 364-377 | 14 | |
| α-helix | 385-409 | 25 | |
| α-helix | 416-430 | 15 | |
| α-helix | 435-443 | 9 |
| Element | Residues | Length | Sheet |
|---|---|---|---|
| α-helix | 3-13 | 11 | |
| α-helix | 16-20 | 5 | |
| α-helix | 21-25 | 5 | |
| α-helix | 31-59 | 29 | |
| α-helix | 65-96 | 32 | |
| α-helix | 98-101 | 4 | |
| α-helix | 114-140 | 27 | |
| β-strand | 146 | 1 | 1 |
| α-helix | 156-183 | 28 | |
| α-helix | 188-202 | 15 | |
| α-helix | 203-205 | 3 | |
| α-helix | 210-213 | 4 | |
| α-helix | 215-232 | 18 | |
| α-helix | 236-239 | 4 |
| Element | Residues | Length | Sheet |
|---|---|---|---|
| α-helix | 9-19 | 11 | |
| α-helix | 27-36 | 10 | |
| α-helix | 48-50 | 3 | |
| α-helix | 59-81 | 23 | |
| α-helix | 88-91 | 4 | |
| β-strand | 93-95 | 3 | 8 |
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|---|---|---|---|---|
| Nicastrin | A | protein | 709 | Homo sapiens | Q92542 (AlphaFold model) |
| Presenilin-2 | B | protein | 448 | Homo sapiens | P49810 (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) |
>7Y5X_1 Nicastrin (chains A) MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
>7Y5X_2 Presenilin-2 (chains B) MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDP DRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLI YTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLL FLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMA LVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVW TVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGV KLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISI TFGLIFYFSTDNLVRPFMDTLASHQLYI
>7Y5X_3 Gamma-secretase subunit APH-1A (chains C) MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ RSLLCRRQEDSRVMVYSALRIPPED
>7Y5X_4 Gamma-secretase subunit PEN-2 (chains D) MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRS AVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
| ID | Name | Formula | Copies |
|---|---|---|---|
| CLR | Cholesterol | C27 H46 O | 3 |
| 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 |
Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560. Guo, X., Wang, Y., Zhou, J. et al. Nat Commun (2022) 13:6299-6299. DOI 10.1038/s41467-022-33817-5 · 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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