6LQG: Human gamma-secretase

Human gamma-secretase in complex with small molecule Avagacestat. Determined by electron microscopy at 3.1 Å resolution. Released 27 Jan 2021.

Method
Electron microscopy
Resolution
3.1 Å
Organism
Homo sapiens
Chains
4
Atoms
10,855
Mol. weight
184.33 kDa
Ligands
PC1, EN9, NAG, CLR
Released
27 Jan 2021

Explore 6LQG in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6LQG contains 60 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.

Chain A: 29 helices, 27 β-strands

ElementResiduesLengthSheet
α-helix37-404
β-strand42-4431
β-strand47-4931
β-strand53-5422
β-strand59-6022
β-strand6113
α-helix64-652
β-strand69-7571
α-helix79-868
β-strand94-9961
α-helix105-1139
β-strand118-12471
α-helix129-1302
β-strand13514
β-strand16814
β-strand17513
β-strand181-18331
α-helix186-19914
β-strand212-21871
α-helix227-23913
β-strand248-25032
β-strand253-25975
β-strand275-28175
α-helix295-2995
α-helix300-31314
β-strand324-33075
α-helix333-3364
α-helix338-34811
α-helix356-3583
β-strand359-36575
β-strand375-37955
α-helix384-3863
α-helix388-40619
β-strand412-41435
α-helix422-4232
α-helix427-4304
β-strand437-44265
α-helix460-4634
α-helix473-4764
α-helix479-4813
α-helix484-50118
α-helix515-52612
α-helix540-5423
α-helix550-5523
α-helix562-57514
β-strand577-57936
α-helix583-5875
β-strand601-60556
α-helix609-6102
β-strand619-62356
β-strand626-63055
α-helix634-6374
β-strand649-65132
β-strand657-66371
α-helix666-69227
α-helix694-6974
Chain B: 15 helices, 3 β-strands
ElementResiduesLengthSheet
α-helix79-10224
α-helix105-1073
α-helix125-15531
α-helix159-17214
α-helix173-1775
α-helix178-18811
β-strand193-19427
α-helix195-21420
α-helix219-23921
α-helix243-26220
α-helix267-27711
β-strand287-28938
β-strand380-38238
α-helix383-39816
α-helix405-42824
α-helix439-44810
α-helix449-4535
α-helix454-4629
Chain C: 10 helices, 1 β-strand
ElementResiduesLengthSheet
α-helix3-1311
α-helix15-206
α-helix21-255
α-helix29-5931
α-helix66-10237
α-helix114-13825
β-strand14611
α-helix156-18328
α-helix189-20214
α-helix215-23117
α-helix236-2427
Chain D: 6 helices, 1 β-strand
ElementResiduesLengthSheet
α-helix10-2011
α-helix21-233
α-helix27-3812
α-helix39-435
α-helix50-8031
α-helix88-914
β-strand93-9537

Molecules and chains

MoleculeChainsTypeLengthOrganismUniProt
NicastrinAprotein709Homo sapiensQ92542 (AlphaFold model)
Presenilin-1Bprotein467Homo sapiensP49768 (AlphaFold model)
Gamma-secretase subunit APH-1ACprotein265Homo sapiensQ96BI3 (AlphaFold model)
Gamma-secretase subunit PEN-2Dprotein143Homo sapiensQ9NZ42 (AlphaFold model)
Sequence of entity 1 (A), FASTA
>6LQG_1 Nicastrin (chains A)
MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
Sequence of entity 2 (B), FASTA
>6LQG_2 Presenilin-1 (chains B)
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Sequence of entity 3 (C), FASTA
>6LQG_3 Gamma-secretase subunit APH-1A (chains C)
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
Sequence of entity 4 (D), FASTA
>6LQG_4 Gamma-secretase subunit PEN-2 (chains D)
MASWSHPQFEKGGGARGGSGGGSWSHPQFEKGFDYKDDDDKGTNLERVSNEEKLNLCRKY
YLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIF
QIYRPRWGALGDYLSFTIPLGTP

Ligands and cofactors

IDNameFormulaCopies
PC11,2-diacyl-sn-glycero-3-phosphocholineC44 H88 N O8 P2
EN9(2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoranyl-4-(1,2,4-oxadiazol-3-yl)phenyl]m…C20 H17 Cl F4 N4 O4 S1
NAG2-acetamido-2-deoxy-beta-D-glucopyranoseC8 H15 N O66
CLRCholesterolC27 H46 O3

Primary citation

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:

Browse structure collections

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