8IM7: Nicastrin

Human gamma-secretase treated with ganglioside GM1. Determined by electron microscopy at 3.4 Å resolution. Released 17 Jan 2024.

Method
Electron microscopy
Resolution
3.4 Å
Organism
Homo sapiens
Chains
4
Atoms
10,587
Mol. weight
178.97 kDa
Ligands
CLR, PC1, NAG
Released
17 Jan 2024

Explore 8IM7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8IM7 contains 67 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.

Chain A: 34 helices, 31 β-strands

ElementResiduesLengthSheet
α-helix37-393
β-strand42-4431
β-strand47-4821
β-strand53-5422
β-strand5912
β-strand6113
α-helix64-652
β-strand69-7681
α-helix81-833
α-helix84-885
β-strand94-9961
α-helix105-1128
β-strand118-12471
β-strand13514
α-helix143-1453
α-helix154-1563
β-strand16814
α-helix171-1733
β-strand17513
β-strand180-18341
α-helix187-19913
α-helix203-2053
α-helix206-2094
β-strand212-21871
α-helix227-23610
β-strand248-25032
β-strand253-25975
α-helix268-2703
β-strand275-28175
α-helix295-2995
α-helix300-31314
β-strand324-33075
α-helix338-34811
α-helix356-3583
β-strand359-36575
β-strand375-37955
α-helix384-3863
α-helix388-40518
β-strand412-41435
α-helix422-4232
α-helix427-4304
β-strand437-44265
α-helix482-50120
α-helix515-52612
α-helix534-5363
α-helix543-5453
α-helix562-57514
β-strand577-57936
α-helix583-5875
α-helix589-5913
β-strand60117
β-strand604-60526
α-helix6081
β-strand60918
α-helix6101
β-strand61618
β-strand619-62246
β-strand62317
β-strand626-63055
α-helix633-6353
β-strand649-65132
α-helix6521
β-strand657-66371
α-helix666-69227
α-helix694-6974
Chain B: 13 helices, 3 β-strands
ElementResiduesLengthSheet
α-helix83-10321
α-helix125-15430
α-helix159-17113
α-helix172-1776
α-helix178-18912
β-strand193-19429
α-helix195-21420
α-helix220-23920
α-helix243-25917
β-strand287-289310
β-strand380-382310
α-helix383-39816
α-helix403-42826
α-helix435-44814
α-helix449-4535
α-helix454-46310
Chain C: 13 helices, 1 β-strand
ElementResiduesLengthSheet
α-helix3-1311
α-helix15-206
α-helix21-255
α-helix29-6032
α-helix65-9531
α-helix99-1024
α-helix114-13421
β-strand14611
α-helix157-18327
α-helix188-20215
α-helix203-2053
α-helix210-2123
α-helix215-23117
α-helix236-2405
Chain D: 7 helices, 1 β-strand
ElementResiduesLengthSheet
α-helix8-1912
α-helix20-223
α-helix27-359
α-helix39-424
α-helix50-589
α-helix60-8021
α-helix88-914
β-strand93-9539

Molecules and chains

MoleculeChainsTypeLengthOrganismUniProt
NicastrinAprotein709Homo sapiensQ92542 (AlphaFold model)
Presenilin-1 CTF12Bprotein467Homo sapiensP49768 (AlphaFold model)
Gamma-secretase subunit APH-1ACprotein265Homo sapiensQ96BI3 (AlphaFold model)
Gamma-secretase subunit PEN-2Dprotein101Homo sapiensQ9NZ42 (AlphaFold model)
Sequence of entity 1 (A), FASTA
>8IM7_1 Nicastrin (chains A)
MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
Sequence of entity 2 (B), FASTA
>8IM7_2 Presenilin-1 CTF12 (chains B)
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Sequence of entity 3 (C), FASTA
>8IM7_3 Gamma-secretase subunit APH-1A (chains C)
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
Sequence of entity 4 (D), FASTA
>8IM7_4 Gamma-secretase subunit PEN-2 (chains D)
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRS
AVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP

Ligands and cofactors

IDNameFormulaCopies
CLRCholesterolC27 H46 O2
PC11,2-diacyl-sn-glycero-3-phosphocholineC44 H88 N O8 P2
NAG2-acetamido-2-deoxy-beta-D-glucopyranoseC8 H15 N O66

Primary citation

Preferential Regulation of Gamma-Secretase-Mediated Cleavage of APP by Ganglioside GM1 Reveals a Potential Therapeutic Target for Alzheimer's Disease. Wang, X., Zhou, R., Sun, X. et al. Adv Sci (Weinh) (2023) 10:e2303411-e2303411. DOI 10.1002/advs.202303411 · PubMed

Other PDB entries of the same protein (UniProt Q92542 (AlphaFold model), which also has an AlphaFold model), best resolution first:

Browse structure collections

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