8WE9: PDB entry 8WE9

Human L-type voltage-gated calcium channel Cav1.2 (Class I) in the presence of pinaverium at 3.0 Angstrom resolution. Determined by electron microscopy at 3.0 Å resolution. Released 6 Dec 2023.

Method: Electron microscopy
Resolution: 3.0 Å
Organism: Homo sapiens
Chains: 3
Atoms: 20,730
Mol. weight: 432.58 kDa
Ligands: CLR, 3PE, CA, PT5
Released: 6 Dec 2023

Explore 8WE9 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8WE9 contains 123 α-helices and 81 β-strands across 3 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: 68 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	127-143	17
α-helix	154-181	28
α-helix	194-216	23
α-helix	240-245	6
α-helix	246-250	5
α-helix	252-261	10
α-helix	267-269	3
α-helix	272-285	14
β-strand	296-300	5	1
β-strand	315	1	1
α-helix	324-326	3
β-strand	330-334	5	1
α-helix	351-360	10
α-helix	365-376	12
α-helix	381-392	12
α-helix	396-418	23
α-helix	421-436	16
α-helix	438-443	6
α-helix	511-520	10
α-helix	526-541	16
α-helix	550-578	29
α-helix	580-583	4
α-helix	587-607	21
α-helix	617-630	14
α-helix	635-646	12
α-helix	651-673	23
α-helix	692-704	13
α-helix	708-717	10
α-helix	726-729	4
α-helix	730-746	17
α-helix	748-781	34
α-helix	900-918	19
α-helix	929-972	24
α-helix	988-1001	14
α-helix	1013-1016	4
α-helix	1018-1020	3
α-helix	1024-1028	5
α-helix	1035-1048	14
α-helix	1051-1071	21
β-strand	1076-1078	3	2
α-helix	1086-1088	3
β-strand	1092-1096	5	3
α-helix	1097-1099	3
β-strand	1104-1108	5	3
β-strand	1111-1113	3	2
α-helix	1121-1132	12
α-helix	1137-1146	10
α-helix	1160-1162	3
α-helix	1163-1169	7
α-helix	1170-1176	7
α-helix	1177-1193	17
α-helix	1206-1214	9
α-helix	1218-1220	3
α-helix	1227-1235	9
α-helix	1239-1257	19
α-helix	1265-1300	36
α-helix	1302-1320	19
α-helix	1374-1376	3
α-helix	1381-1384	4
α-helix	1385-1389	5
α-helix	1394-1407	14
α-helix	1411-1429	19
β-strand	1433	1	4
α-helix	1450-1462	13
α-helix	1466-1472	7
β-strand	1477	1	5
α-helix	1478	1
β-strand	1479	1	4
α-helix	1480	1
β-strand	1495	1	5
α-helix	1500-1525	26
α-helix	1539-1541	3
α-helix	1543-1549	7
α-helix	1550-1552	3
α-helix	1568-1570	3
α-helix	1586-1593	8
α-helix	1607-1617	11
α-helix	1627-1634	8
α-helix	1643-1645	3

Chain C: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	39-45	7
α-helix	48-51	4
α-helix	58-60	3
β-strand	64	1	23
β-strand	65	1	24
β-strand	71	1	25
β-strand	84	1	25
β-strand	93	1	23
β-strand	103-104	2	26
β-strand	107	1	27
β-strand	115	1	27
β-strand	118-119	2	26
α-helix	121-127	7
α-helix	153-155	3
β-strand	172	1	24
β-strand	180-183	4	28
α-helix	192-208	17
α-helix	247-251	5
α-helix	258-263	6
β-strand	268-269	2	28
β-strand	288-291	4	28
α-helix	299-305	7
α-helix	316-325	10
α-helix	330-332	3
β-strand	335-336	2	28
α-helix	342-359	18

Chain D: 43 helices, 56 β-strands

Element	Residues	Length	Sheet
α-helix	30-52	23
α-helix	55-58	4
α-helix	60-63	4
α-helix	65-67	3
β-strand	68-72	5	6
α-helix	75-109	35
α-helix	118-120	3
β-strand	122	1	7
β-strand	126	1	8
β-strand	142	1	7
β-strand	150-151	2	9
β-strand	158-159	2	9
β-strand	160	1	10
β-strand	165-167	3	8
α-helix	177-185	9
α-helix	189-199	11
β-strand	206-210	5	8
β-strand	215-217	3	8
β-strand	220	1	10
α-helix	238-240	3
α-helix	242-248	7
β-strand	252	1	11
β-strand	255-259	5	12
α-helix	262-264	3
α-helix	267-279	13
α-helix	280-282	3
β-strand	288-289	2	13
β-strand	290-294	5	12
β-strand	298-300	3	12
β-strand	308-309	2	13
α-helix	312-322	11
α-helix	333-343	11
β-strand	355	1	11
β-strand	356-362	7	12
α-helix	370-375	6
β-strand	382-389	8	12
α-helix	397-405	9
β-strand	410-413	4	12
α-helix	416-418	3
α-helix	419-422	4
α-helix	427-430	4
α-helix	432-435	4
α-helix	438-441	4
β-strand	450-451	2	14
β-strand	458-461	4	14
β-strand	464-467	4	8
β-strand	484-490	7	8
β-strand	491-493	3	14
α-helix	494-497	4
β-strand	511-515	5	15
β-strand	520	1	16
β-strand	521-523	3	15
α-helix	531-533	3
β-strand	560	1	16
α-helix	561-564	4
α-helix	570-579	10
β-strand	584-593	10	15
β-strand	599	1	17
β-strand	600-611	12	15
β-strand	618-622	5	15
β-strand	629-633	5	6
α-helix	638-647	10
α-helix	653-656	4
β-strand	658-659	2	18
α-helix	670-672	3
α-helix	676-688	13
α-helix	700-715	16
α-helix	716-720	5
β-strand	732-736	5	18
β-strand	742-743	2	18
α-helix	749-751	3
α-helix	758-760	3
α-helix	762-769	8
β-strand	773	1	19
β-strand	774-776	3	18
β-strand	793-797	5	18
β-strand	801	1	20
β-strand	806	1	20
β-strand	810-814	5	18
α-helix	819-826	8
β-strand	848-854	7	21
β-strand	858-862	5	21
α-helix	865-869	5
β-strand	874	1	21
α-helix	875-878	4
α-helix	880-888	9
β-strand	892-899	8	17
β-strand	903-904	2	22
β-strand	972-973	2	22
β-strand	976-983	8	17
β-strand	989-994	6	21
β-strand	1001-1007	7	21
α-helix	1008	1
β-strand	1011	1	19
β-strand	1013-1019	7	21
α-helix	1021-1023	3
β-strand	1036-1037	2	17
α-helix	1043-1045	3
α-helix	1050-1052	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Voltage-dependent L-type calcium channel subunit alpha-1C	A	protein	2201	Homo sapiens	Q13936 (AlphaFold model)
Voltage-dependent calcium channel subunit alpha-2/delta-1	D	protein	1103	Homo sapiens	P54289 (AlphaFold model)
Voltage-dependent L-type calcium channel subunit beta-3	C	protein	484	Homo sapiens	P54284 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8WE9_1 Voltage-dependent L-type calcium channel subunit alpha-1C (chains A)
MVNENTRMYIPEENHQGSNYGSPRPAHANMNANAAAGLAPEHIPTPGAALSWQAAIDAAR
QAKLMGSAGNATISTVSSTQRKRQQYGKPKKQGSTTATRPPRALLCLTLKNPIRRACISI
VEWKPFEIIILLTIFANCVALAIYIPFPEDDSNATNSNLERVEYLFLIIFTVEAFLKVIA
YGLLFHPNAYLRNGWNLLDFIIVVVGLFSAILEQATKADGANALGGKGAGFDVKALRAFR
VLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFMGKMHKTCYN
QEGIADVPAEDDPSPCALETGHGRQCQNGTVCKPGWDGPKHGITNFDNFAFAMLTVFQCI
TMEGWTDVLYWVNDAVGRDWPWIYFVTLIIIGSFFVLNLVLGVLSGEFSKEREKAKARGD
FQKLREKQQLEEDLKGYLDWITQAEDIDPENEDEGMDEEKPRNMSMPTSETESVNTENVA
GGDIEGENCGARLAHRISKSKFSRYWRRWNRFCRRKCRAAVKSNVFYWLVIFLVFLNTLT
IASEHYNQPNWLTEVQDTANKALLALFTAEMLLKMYSLGLQAYFVSLFNRFDCFVVCGGI
LETILVETKIMSPLGISVLRCVRLLRIFKITRYWNSLSNLVASLLNSVRSIASLLLLLFL
FIIIFSLLGMQLFGGKFNFDEMQTRRSTFDNFPQSLLTVFQILTGEDWNSVMYDGIMAYG
GPSFPGMLVCIYFIILFICGNYILLNVFLAIAVDNLADAESLTSAQKEEEEEKERKKLAR
TASPEKKQELVEKPAVGESKEEKIELKSITADGESPPATKINMDDLQPNENEDKSPYPNP
ETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEASAFFIFSSNNRFRLQCHRIVNDT
IFTNLILFFILLSSISLAAEDPVQHTSFRNHILGNADYVFTSIFTLEIILKMTAYGAFLH
KGSFCRNYFNILDLLVVSVSLISFGIQSSAINVVKILRVLRVLRPLRAINRAKGLKHVVQ
CVFVAIRTIGNIVIVTTLLQFMFACIGVQLFKGKLYTCSDSSKQTEAECKGNYITYKDGE
VDHPIIQPRSWENSKFDFDNVLAAMMALFTVSTFEGWPELLYRSIDSHTEDKGPIYNYRV
EISIFFIIYIIIIAFFMMNIFVGFVIVTFQEQGEQEYKNCELDKNQRQCVEYALKARPLR
RYIPKNQHQYKVWYVVNSTYFEYLMFVLILLNTICLAMQHYGQSCLFKIAMNILNMLFTG
LFTVEMILKLIAFKPKGYFSDPWNVFDFLIVIGSIIDVILSETNHYFCDAWNTFDALIVV
GSIVDIAITEVNPAEHTQCSPSMNAEENSRISITFFRLFRVMRLVKLLSRGEGIRTLLWT
FIKSFQALPYVALLIVMLFFIYAVIGMQVFGKIALNDTTEINRNNNFQTFPQAVLLLFRC
ATGEAWQDIMLACMPGKKCAPESEPSNSTEGETPCGSSFAVFYFISFYMLCAFLIINLFV
AVIMDNFDYLTRDWSILGPHHLDEFKRIWAEYDPEAKGRIKHLDVVTLLRRIQPPLGFGK
LCPHRVACKRLVSMNMPLNSDGTVMFNATLFALVRTALRIKTEGNLEQANEELRAIIKKI
WKRTSMKLLDQVVPPAGDDEVTVGKFYATFLIQEYFRKFKKRKEQGLVGKPSQRNALSLQ
AGLRTLHDIGPEIRRAISGDLTAEEELDKAMKEAVSAASEDDIFRRAGGLFGNHVSYYQS
DGRSAFPQTFTTQRPLHINKAGSSQGDTESPSHEKLVDSTFTPSSYSSTGSNANINNANN
TALGRLPRPAGYPSTVSTVEGHGPPLSPAIRVQEVAWKLSSNRERHVPMCEDLELRRDSG
SAGTQAHCLLLRKANPSRCHSRESQAAMAGQEETSQDETYEVKMNHDTEACSEPSLLSTE
MLSYQDDENRQLTLPEEDKRDIRQSPKRGFLRSASLGRRASFHLECLKRQKDRGGDISQK
TVLPLHLVHHQALAVAGLSPLLQRSHSPASFPRPFATPPATPGSRGWPPQPVPTLRLEGV
ESSEKLNSSFPSIHCGSWAETTPGGGGSSAARRVRPVSLMVPSQAGAPGRQFHGSASSLV
EAVLISEGLGQFAQDPKFIEVTTQELADACDMTIEEMESAADNILSGGAPQSPNGALLPF
VNCRDAGQDRAGGEEDAGCVRARGRPSEEELQDSRVYVSSL

Sequence of entity 2 (D), FASTA

>8WE9_2 Voltage-dependent calcium channel subunit alpha-2/delta-1 (chains D)
MAAGCLLALTLTLFQSLLIGPSSEEPFPSAVTIKSWVDKMQEDLVTLAKTASGVNQLVDI
YEKYQDLYTVEPNNARQLVEIAARDIEKLLSNRSKALVRLALEAEKVQAAHQWREDFASN
EVVYYNAKDDLDPEKNDSEPGSQRIKPVFIEDANFGRQISYQHAAVHIPTDIYEGSTIVL
NELNWTSALDEVFKKNREEDPSLLWQVFGSATGLARYYPASPWVDNSRTPNKIDLYDVRR
RPWYIQGAASPKDMLILVDVSGSVSGLTLKLIRTSVSEMLETLSDDDFVNVASFNSNAQD
VSCFQHLVQANVRNKKVLKDAVNNITAKGITDYKKGFSFAFEQLLNYNVSRANCNKIIML
FTDGGEERAQEIFNKYNKDKKVRVFTFSVGQHNYDRGPIQWMACENKGYYYEIPSIGAIR
INTQEYLDVLGRPMVLAGDKAKQVQWTNVYLDALELGLVITGTLPVFNITGQFENKTNLK
NQLILGVMGVDVSLEDIKRLTPRFTLCPNGYYFAIDPNGYVLLHPNLQPKPIGVGIPTIN
LRKRRPNIQNPKSQEPVTLDFLDAELENDIKVEIRNKMIDGESGEKTFRTLVKSQDERYI
DKGNRTYTWTPVNGTDYSLALVLPTYSFYYIKAKLEETITQARYSETLKPDNFEESGYTF
IAPRDYCNDLKISDNNTEFLLNFNEFIDRKTPNNPSCNADLINRVLLDAGFTNELVQNYW
SKQKNIKGVKARFVVTDGGITRVYPKEAGENWQENPETYEDSFYKRSLDNDNYVFTAPYF
NKSGPGAYESGIMVSKAVEIYIQGKLLKPAVVGIKIDVNSWIENFTKTSIRDPCAGPVCD
CKRNSDVMDCVILDDGGFLLMANHDDYTNQIGRFFGEIDPSLMRHLVNISVYAFNKSYDY
QSVCEPGAAPKQGAGHRSAYVPSVADILQIGWWATAAAWSILQQFLLSLTFPRLLEAVEM
EDDDFTASLSKQSCITEQTQYFFDNDSKSFSGVLDCGNCSRIFHGEKLMNTNLIFIMVES
KGTCPCDTRLLIQAEQTSDGPNPCDMVKQPRYRKGPDVCFDNNVLEDYTDCGGVSGLNPS
LWYIIGIQFLLLWLVSGSTHRLL

Sequence of entity 3 (C), FASTA

>8WE9_3 Voltage-dependent L-type calcium channel subunit beta-3 (chains C)
MYDDSYVPGFEDSEAGSADSYTSRPSLDSDVSLEEDRESARREVESQAQQQLERAKHKPV
AFAVRTNVSYCGVLDEECPVQGSGVNFEAKDFLHIKEKYSNDWWIGRLVKEGGDIAFIPS
PQRLESIRLKQEQKARRSGNPSSLSDIGNRRSPPPSLAKQKQKQAEHVPPYDVVPSMRPV
VLVGPSLKGYEVTDMMQKALFDFLKHRFDGRISITRVTADLSLAKRSVLNNPGKRTIIER
SSARSSIAEVQSEIERIFELAKSLQLVVLDADTINHPAQLAKTSLAPIIVFVKVSSPKVL
QRLIRSRGKSQMKHLTVQMMAYDKLVQCPPESFDVILDENQLEDACEHLAEYLEVYWRAT
HHPAPGPGLLGPPSAIPGLQNQQLLGERGEEHSPLERDSLMPSDEASESSRQAWTGSSQR
SSRHLEEDYADAYQDLYQPHRQHTSGLPSANGHDPQDRLLAQDSEHNHSDRNWQRNRPWP
KDSY

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	3
3PE	1,2-Distearoyl-sn-glycerophosphoethanolamine	C41 H82 N O8 P	1
CA	Calcium ion	Ca	2
PT5	[(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4…	C47 H85 O19 P3	1
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	3

Primary citation

Structural basis for human Ca v 1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Gao, S., Yao, X., Chen, J. et al. Cell (2023) 186:5363-5374.e16. DOI 10.1016/j.cell.2023.10.007 · PubMed

Other PDB entries of the same protein (UniProt Q13936 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2F3Y 1.45 Å, Calmodulin/IQ domain complex
2F3Z 1.6 Å, Calmodulin/IQ-AA domain complex
6DAD 1.65 Å, 1.65 Angstrom crystal structure of the N97I Ca/CaM:CaV1.2 IQ domain complex
6U3A 1.65 Å, 1.65 Angstrom crystal structure of the N97S Ca-CaM:CaV1.2 IQ domain complex
5V2Q 1.7 Å, CaV beta2a subunit: CaV1.2 AID-CEN complex
6U3B 1.7 Å, 1.7 Angstrom crystal structure of the Q135P Ca-CaM:CaV1.2 IQ domain complex
6U3D 1.75 Å, 1.75 Angstrom crystal structure of the N53I Ca-CaM:CaV1.2 IQ domain complex
1T0J 2.0 Å, Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and…
2BE6 2.0 Å, 2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex
5V2P 2.0 Å, CaV beta2a subunit: CaV1.2 AID-CAP complex
6DAE 2.0 Å, 2.0 Angstrom crystal structure of the D95V Ca/CaM:CaV1.2 IQ domain complex
3G43 2.1 Å, Crystal structure of the calmodulin-bound Cav1.2 C-terminal regulatory domain dimer

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