8F0S: VSD4-NaV1.7-NaVPas channel chimera

Structure of VSD4-NaV1.7-NaVPas channel chimera bound to the hybrid inhibitor GNE-9296. Determined by electron microscopy at 3.1 Å resolution. Released 12 Apr 2023.

Method
Electron microscopy
Resolution
3.1 Å
Organisms
Homo sapiens, Periplaneta americana, Diguetia canities
Chains
2
Atoms
9,734
Mol. weight
196.74 kDa
Ligands
Y01, PEE, X80, NAG
Released
12 Apr 2023

Explore 8F0S in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8F0S contains 78 α-helices and 20 β-strands across 2 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: 78 helices, 13 β-strands

ElementResiduesLengthSheet
α-helix130-1378
α-helix140-15819
α-helix160-1612
α-helix163-18725
α-helix196-1983
α-helix200-21718
α-helix225-24016
α-helix244-25714
α-helix259-27921
α-helix283-2853
β-strand287-29041
α-helix291-2933
α-helix303-3119
α-helix313-3153
β-strand31611
α-helix325-3273
α-helix335-3384
β-strand341-34441
α-helix351-3544
α-helix361-37313
α-helix377-38812
α-helix390-3923
α-helix393-3997
α-helix400-4089
α-helix409-42921
α-helix519-53820
β-strand543-54422
α-helix545-57228
α-helix575-5784
α-helix582-59918
α-helix612-6143
α-helix615-6184
α-helix619-6224
α-helix625-63612
α-helix638-66326
α-helix666-6694
α-helix671-6733
α-helix679-6802
α-helix687-69913
α-helix703-71210
α-helix717-7248
α-helix725-7328
α-helix733-74311
α-helix843-85412
α-helix856-87318
α-helix880-8823
α-helix884-91229
α-helix914-9174
α-helix921-94222
α-helix944-9474
α-helix948-9514
α-helix952-9587
α-helix959-9635
α-helix968-100437
β-strand1009-101243
β-strand101813
α-helix1019-10202
β-strand102614
α-helix1027-10326
β-strand1036-103943
α-helix10401
α-helix1047-105913
α-helix1063-10719
β-strand107814
α-helix1086-10883
α-helix1089-10957
α-helix1096-11005
α-helix1106-112217
α-helix1131-114414
α-helix1158-116811
α-helix1170-118920
α-helix1196-122429
α-helix1225-12306
α-helix1232-125625
α-helix1261-12677
α-helix1268-12747
α-helix1276-12794
α-helix1284-129411
α-helix1296-132025
α-helix1324-13263
β-strand132715
β-strand133015
α-helix1339-134911
α-helix1355-13639
α-helix1369-13713
β-strand137216
β-strand137716
α-helix1384-139411
α-helix1395-14028
α-helix1403-142321
α-helix1427-143610
Chain B: 0 helices, 7 β-strands
ElementResiduesLengthSheet
β-strand1417
β-strand1912
β-strand2517
β-strand28-3148
β-strand34-3748
β-strand38-4472
β-strand50-5672

Molecules and chains

MoleculeChainsTypeLengthOrganismUniProt
Sodium channel protein PaFPC1,Sodium channel protein type 9 subunit alpha chimeraAprotein1608Homo sapiens, Periplaneta americanaD0E0C2 (AlphaFold model), Q15858 (AlphaFold model)
Beta-diguetoxin-Dc1aBprotein71Diguetia canitiesP49126 (AlphaFold model)
Sequence of entity 1 (A), FASTA
>8F0S_1 Sodium channel protein PaFPC1,Sodium channel protein type 9 subunit alpha chimera (chains A)
MWSHPQFEKGGGSGGGSGGSAWSHPQFEKGGSGGDYKDDDDKGGSGGDYKDDDDKMADNS
PLIREERQRLFRPYTRAMLTAPSAQPAKENGKTEENKDNSRDKGRGANKDRDGSAHPDQA
LEQGSRLPARMRNIFPAELASTPLEDFDPFYKNKKTFVVVTKAGDIFRFSGEKSLWMLDP
FTPIRRVAISTMVQPIFSYFIMITILIHCIFMIMPATQTTYILELVFLSIYTIEVVVKVL
ARGFILHPFAYLRDPWNWLDFLVTLIGYITLVVDLGHLYALRAFRVLRSWRTVTIVPGWR
TIVDALSLSITSLKDLVLLLLFSLSVFALIGLQLFMGNLKHKCVKHFPADGSWGNFTDER
WFNYTSNSSHWYIPDDWIEYPLCGNSSGAGMCPPGYTCLQGYGGNPNYGYTSFDTFGWAF
LSVFRLVTLDYWEDLYQLALRSAGPWHILFFIIVVFYGTFCFLNFILAVVVMSYTHMVKR
ADEEKAAERELKKEKKAASVANNTANGQEQTTIEMNGDEAVVIDNNDQAARQQSDPETPA
PSVTQRLTDFLCVWDCCVPWQKLQGAIGAVVLSPFFELFIAVIIVLNITFMALDHHDMNI
EFERILRTGNYIFTSIYIVEAVLKIIALSPKFYFKDSWNVFDFIIVVFAILELGLEGVQG
LSVFRSFRLLRVFRLAKFWPTLNNFMSVMTKSYGAFVNVMYVMFLLLFIFAIIGMQLFGM
NYIDNMERFPDGDLPRWNFTDFLHSFMIVFRALCGEWIESMWDCMLVGDWSCIPFFVAVF
FVGNLVILNLLIALLLNNYGSFCTSPTSDEEDSKDEDALAQIVRIFKRFKPNLNAVKLSP
MKPDSEDIVESQEIQGNNIADAEDVLAGEFPPDCCCNAFYKCFPSRPARDSSVQRMWSNI
RRVCFLLAKNKYFQKFVTAVLVITSVLLALEDIYLPQRPVLVNITLYVDYVLTAFFVIEM
IIMLFAVGFKKYFTSKWYWLDFIVVVAYLLNFVLMCAGIEALQTLRLLRVFRLFRPLSKV
NGMQVVTSTLVEAVPHIFNVILVGIFFWLVFAIMGVQLFAGKFYKCVDENSTVLSHEITM
DRNDCLHENYTWENSPMNFDHVGNAYLSLLQVATFKGWLQIMNDAIDSREVHKQPIRETN
IYMYLYFIFFIVFGSFFILKLFVCILIDIFRQQRRKAEGLSATDSRTQLIYRRAVMRTMS
AKPVKRIPKPGNKIQGCIFDLVTNQAFDISIMVLICLNMVTMMVEKEGQSQHMTEVLYWI
NVVFIILFTGECVLKLISLRHYYFTVGWNIFDFVVVIISIVGMFLADLIETYFVSPTLFR
VIRLARIGRILRLVKGAKGIRLLLLALRKALRTLFNVSFLLFVIMFVYAVFGMEFFMHIR
DAGAIDDVYNFKTFGQSIILLFQLATSAGWDGVYFAIANEEDCRAPDHELGYPGNCGSRA
LGIAYLVSYLIITCLVVINMYAAVILDYVLEVYEDSKEGLTDDDYDMFFEVWQQFDPEAT
QYIRYDQLSELLEALQPPLQVQKPNKYKILSMNIPICKDDHIFYKDVLEALVKDVFSRRG
SPVEAGDVQAPNVDEAEYKPVSSTLQRQREEYCVRLIQNAWRKHKQQN
Sequence of entity 2 (B), FASTA
>8F0S_2 Beta-diguetoxin-Dc1a (chains B)
HHHHHHGENLYFQGSAKDGDVEGPAGCKKYDVECDSGECCQKQYLWYKWRPLDCRCLKSG
FFSSKCVCRDV

Ligands and cofactors

IDNameFormulaCopies
Y01Cholesterol hemisuccinateC31 H50 O41
PEE1,2-dioleoyl-sn-glycero-3-phosphoethanolamineC41 H78 N O8 P1
X805-chloro-4-(cyclopentylmethoxy)-N-(4-{[(1S,2S)-2-(dimethylamino)cyclohexyl]amin…C27 H34 Cl F2 N3 O4 S1
NAG2-acetamido-2-deoxy-beta-D-glucopyranoseC8 H15 N O64

Primary citation

Cryo-EM reveals an unprecedented binding site for Na V 1.7 inhibitors enabling rational design of potent hybrid inhibitors. Kschonsak, M., Jao, C.C., Arthur, C.P. et al. Elife (2023) 12. DOI 10.7554/eLife.84151 · PubMed

Other PDB entries of the same protein (UniProt D0E0C2 (AlphaFold model), which also has an AlphaFold model), best resolution first:

Browse structure collections

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