7OPL: DNA Polymerase alpha - primase

CryoEM structure of DNA Polymerase alpha - primase bound to SARS CoV nsp1. Determined by electron microscopy at 4.12 Å resolution. Released 10 Nov 2021.

Method: Electron microscopy
Resolution: 4.12 Å
Organisms: Homo sapiens, Severe acute respiratory syndrome coronavirus
Chains: 5
Atoms: 19,743
Mol. weight: 308.54 kDa
Ligands: SF4, ZN
Released: 10 Nov 2021

Explore 7OPL in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7OPL contains 126 α-helices and 110 β-strands across 5 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: 56 helices, 49 β-strands

Element	Residues	Length	Sheet
β-strand	340-349	10	1
β-strand	359-367	9	1
β-strand	372-380	9	1
β-strand	385-391	7	2
β-strand	394-396	3	3
α-helix	397	1
β-strand	403-407	5	3
α-helix	410-416	7
α-helix	417-421	5
α-helix	422-424	3
β-strand	431	1	2
β-strand	434-436	3	2
β-strand	438	1	4
β-strand	451-457	7	2
α-helix	462-465	4
β-strand	473-477	5	2
α-helix	483-490	8
β-strand	498-502	5	1
β-strand	505	1	1
β-strand	512	1	5
β-strand	516	1	1
β-strand	519-520	2	1
α-helix	523-525	3
β-strand	526-528	3	1
α-helix	533-536	4
β-strand	537-545	9	6
β-strand	559-568	10	6
α-helix	573-575	3
β-strand	581-583	3	6
β-strand	585-586	2	6
α-helix	593-595	3
α-helix	598-605	8
β-strand	610-611	2	6
α-helix	615-629	15
β-strand	633-636	4	6
α-helix	643-654	12
α-helix	659-662	4
β-strand	665	1	5
α-helix	670-671	2
β-strand	690-692	3	6
α-helix	693-700	8
α-helix	708-711	4
α-helix	712-716	5
α-helix	728-731	4
α-helix	735-759	25
α-helix	761-772	12
α-helix	776-781	6
α-helix	784-798	15
β-strand	801	1	4
α-helix	803-807	5
α-helix	845-847	3
β-strand	850-852	3	7
β-strand	856-858	3	7
β-strand	860	1	8
α-helix	864-872	9
α-helix	901-903	3
α-helix	907-908	2
α-helix	910-930	21
α-helix	936-960	25
α-helix	970-993	24
β-strand	997-1001	5	7
β-strand	1006-1009	4	7
α-helix	1015-1032	18
β-strand	1039	1	8
β-strand	1043-1051	9	7
β-strand	1054-1062	9	7
α-helix	1064-1066	3
β-strand	1068-1075	8	7
α-helix	1086-1099	14
α-helix	1105-1125	21
α-helix	1130-1133	4
β-strand	1135-1138	4	9
α-helix	1143-1145	3
α-helix	1153-1164	12
α-helix	1173	1
β-strand	1174-1177	4	9
β-strand	1178	1	10
β-strand	1181	1	11
α-helix	1188-1191	4
β-strand	1193	1	10
α-helix	1195-1200	6
β-strand	1205	1	11
α-helix	1208-1214	7
α-helix	1217-1224	8
α-helix	1232-1239	8
α-helix	1243-1248	6
α-helix	1269-1272	4
β-strand	1279-1282	4	12
β-strand	1289-1292	4	12
β-strand	1296	1	13
α-helix	1300-1302	3
β-strand	1305	1	13
α-helix	1306-1308	3
α-helix	1319-1321	3
α-helix	1323-1342	20
β-strand	1346-1348	3	14
β-strand	1356-1357	2	14
α-helix	1369-1371	3
β-strand	1379-1381	3	14
α-helix	1385-1399	15
α-helix	1401-1404	4
α-helix	1411-1420	10
α-helix	1424-1441	18
β-strand	1448-1450	3	15
α-helix	1452-1455	4

Chain B: 14 helices, 37 β-strands

Element	Residues	Length	Sheet
β-strand	170-174	5	16
β-strand	194-195	2	17
α-helix	213-235	23
β-strand	247	1	18
β-strand	255-259	5	19
β-strand	270-273	4	19
α-helix	276-279	4
β-strand	283-285	3	19
β-strand	295-296	2	20
β-strand	301-302	2	19
β-strand	304	1	21
β-strand	307	1	22
β-strand	308	1	18
β-strand	315	1	22
β-strand	319	1	21
α-helix	321-326	6
β-strand	327	1	23
α-helix	328-329	2
α-helix	332-335	4
β-strand	340-346	7	16
α-helix	358-370	13
β-strand	374-378	5	16
β-strand	383	1	24
α-helix	387-390	4
α-helix	398-412	15
β-strand	419-423	5	16
β-strand	428	1	24
β-strand	435	1	25
β-strand	437	1	26
α-helix	438	1
α-helix	447-452	6
β-strand	453-455	3	16
β-strand	458	1	26
β-strand	460-464	5	17
β-strand	467-471	5	17
α-helix	476-483	8
β-strand	485-486	2	20
α-helix	494-504	11
β-strand	507	1	27
α-helix	514-515	2
β-strand	520	1	25
α-helix	522-528	7
β-strand	530	1	27
β-strand	534	1	23
β-strand	537-539	3	17
β-strand	547-551	5	17
β-strand	554-558	5	17
β-strand	564	1	28
β-strand	567	1	28
β-strand	570-576	7	16
β-strand	590-597	8	16

Chain C: 27 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	2-4	3
α-helix	6-8	3
α-helix	9-19	11
α-helix	23-31	9
α-helix	32-34	3
β-strand	43-48	6	29
α-helix	50-52	3
β-strand	54-58	5	29
α-helix	63-73	11
β-strand	77-84	8	29
α-helix	88-93	6
α-helix	95	1
β-strand	101-103	3	29
β-strand	109-111	3	30
α-helix	112-114	3
α-helix	129-131	3
α-helix	133-144	12
α-helix	145-149	5
β-strand	155-159	5	30
β-strand	164-169	6	30
α-helix	172-175	4
α-helix	179-188	10
α-helix	210-225	16
α-helix	226-230	5
α-helix	237-246	10
α-helix	249-251	3
α-helix	252-261	10
α-helix	265-282	18
α-helix	292-301	10
α-helix	307-311	5
β-strand	317-318	2	29
α-helix	319	1
β-strand	323	1	31
β-strand	329	1	32
β-strand	330	1	31
β-strand	333	1	30
β-strand	349	1	32
α-helix	350-358	9
α-helix	382-385	4
α-helix	389-411	23

Chain D: 25 helices, 5 β-strands

Element	Residues	Length	Sheet
β-strand	36-38	3	15
α-helix	39-62	24
α-helix	68-81	14
α-helix	89-110	22
α-helix	114-134	21
α-helix	137-146	10
β-strand	152-153	2	33
α-helix	154-155	2
α-helix	156-169	14
β-strand	184-187	4	33
α-helix	188-191	4
α-helix	192-195	4
β-strand	202-203	2	33
β-strand	206-209	4	33
α-helix	211-240	30
α-helix	247-250	4
α-helix	276-283	8
α-helix	286-298	13
α-helix	303-315	13
α-helix	320-332	13
α-helix	338-341	4
α-helix	342-346	5
α-helix	347-353	7
α-helix	364-366	3
α-helix	367-372	6
α-helix	385-388	4
α-helix	391-400	10
α-helix	405-416	12
α-helix	420-432	13
α-helix	444-454	11

Chain E: 4 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	14-20	7	34
α-helix	23-25	3
α-helix	35-48	14
β-strand	51-55	5	34
α-helix	61-63	3
α-helix	65	1
β-strand	70-73	4	34
β-strand	85-89	5	34
β-strand	103-109	7	34
β-strand	118-123	6	34

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
DNA polymerase alpha catalytic subunit	A	protein	1170	Homo sapiens	P09884 (AlphaFold model)
DNA polymerase alpha subunit B	B	protein	452	Homo sapiens	Q14181 (AlphaFold model)
DNA primase small subunit	C	protein	441	Homo sapiens	P49642 (AlphaFold model)
DNA primase large subunit	D	protein	509	Homo sapiens	P49643 (AlphaFold model)
Non-structural protein 1	E	protein	119	Severe acute respiratory syndrome coronavirus	P0C6U8

Sequence of entity 1 (A), FASTA

>7OPL_1 DNA polymerase alpha catalytic subunit (chains A)
MSAWSHPQFEKGGGSGGGSGGGSWSHPQFEKLEVLFQGPEFGADEEQVFHFYWLDAYEDQ
YNQPGVVFLFGKVWIESAETHVSCCVMVKNIERTLYFLPREMKIDLNTGKETGTPISMKD
VYEEFDEKIATKYKIMKFKSKPVEKNYAFEIPDVPEKSEYLEVKYSAEMPQLPQDLKGET
FSHVFGTNTSSLELFLMNRKIKGPCWLEVKSPQLLNQPVSWCKVEAMALKPDLVNVIKDV
SPPPLVVMAFSMKTMQNAKNHQNEIIAMAALVHHSFALDKAAPKPPFQSHFCVVSKPKDC
IFPYAFKEVIEKKNVKVEVAATERTLLGFFLAKVHKIDPDIIVGHNIYGFELEVLLQRIN
VCKAPHWSKIGRLKRSNMPKLGGRSGFGERNATCGRMICDVEISAKELIRCKSYHLSELV
QQILKTERVVIPMENIQNMYSESSQLLYLLEHTWKDAKFILQIMCELNVLPLALQITNIA
GNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKK
GRKKAAYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASEAQKVTED
GEQEQIPELPDPSLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLILQYDIRQKALKLT
ANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNS
TNLEEVFKLGNKVKSEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYVTKQ
ELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQ
FEINKALTKDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTASQRA
YAPEQLQKQDNLTIDTQYYLAQQIHPVVARICEPIDGIDAVLIATWLGLDPTQFRVHHYH
KDEENDALLGGPAQLTDEEKYRDCERFKCPCPTCGTENIYDNVFDGSGTDMEPSLYRCSN
IDCKASPLTFTVQLSNKLIMDIRRFIKKYYDGWLICEEPTCRNRTRHLPLQFSRTGPLCP
ACMKATLQPEYSDKSLYTQLCFYRYIFDAECALEKLTTDHEKDKLKKQFFTPKVLQDYRK
LKNTAEQFLSRSGYSEVNLSKLFAGCAVKS

Sequence of entity 2 (B), FASTA

>7OPL_2 DNA polymerase alpha subunit B (chains B)
MGSSFSPSATPSQKYNSRSNRGEVVTSFGLAQGVSWSGRGGAGNISLKVLGCPEALTGSY
KSMFQKLPDIREVLTCKIEELGSELKEHYKIEAFTPLLAPAQEPVTLLGQIGCDSNGKLN
NKSVILEGDREHSSGAQIPVDLSELKEYSLFPGQVVIMEGINTTGRKLVATKLYEGVPLP
FYQPTEEDADFEQSMVLVACGPYTTSDSITYDPLLDLIAVINHDRPDVCILFGPFLDAKH
EQVENCLLTSPFEDIFKQCLRTIIEGTRSSGSHLVFVPSLRDVHHEPVYPQPPFSYSDLS
REDKKQVQFVSEPCSLSINGVIFGLTSTDLLFHLGAEEISSSSGTSDRFSRILKHILTQR
SYYPLYPPQEDMAIDYESFYVYAQLPVTPDVLIIPSELRYFVKDVLGCVCVNPGRLTKGQ
VGGTFARLYLRRPAADGAERQSPCIAVQVVRI

Sequence of entity 3 (C), FASTA

>7OPL_3 DNA primase small subunit (chains C)
MHHHHHHHHHHGENLYFQGTSMETFDPTELPELLKLYYRRLFPYSQYYRWLNYGGVIKNY
FQHREFSFTLKDDIYIRYQSFNNQSDLEKEMQKMNPYKIDIGAVYSHRPNQHNTVKLGAF
QAQEKELVFDIDMTDYDDVRRCCSSADICPKCWTLMTMAIRIIDRALKEDFGFKHRLWVY
SGRRGVHCWVCDESVRKLSSAVRSGIVEYLSLVKGGQDVKKKVHLSEKIHPFIRKSINII
KKYFEEYALVNQDILENKESWDKILALVPETIHDELQQSFQKSHNSLQRWEHLKKVASRY
QNNIKNDKYGPWLEWEIMLQYCFPRLDINVSKGINHLLKSPFSVHPKTGRISVPIDLQKV
DQFDPFTVPTISFICRELDAISTNEEEKEENEAESDVKHRTRDYKKTSLAPYVKVFEHFL
ENLDKSRKGELLKKSDLQKDF

Sequence of entity 4 (D), FASTA

>7OPL_4 DNA primase large subunit (chains D)
MEFSGRKWRKLRLAGDQRNASYPHCLQFYLQPPSENISLIEFENLAIDRVKLLKSVENLG
VSYVKGTEQYQSKLESELRKLKFSYRENLEDEYEPRRRDHISHFILRLAYCQSEELRRWF
IQQEMDLLRFRFSILPKDKIQDFLKDSQLQFEAISDEEKTLREQEIVASSPSLSGLKLGF
ESIYKIPFADALDLFRGRKVYLEDGFAYVPLKDIVAIILNEFRAKLSKALALTARSLPAV
QSDERLQPLLNHLSHSYTGQDYSTQGNVGKISLDQIDLLSTKSFPPCMRQLHKALRENHH
LRHGGRMQYGLFLKGIGLTLEQALQFWKQEFIKGKMDPDKFDKGYSYNIRHSFGKEGKRT
DYTPFSCLKIILSNPPSQGDYHGCPFRHSDPELLKQKLQSYKISPGGISQILDLVKGTHY
QVACQKYFEMIHNVDDCGFSLNHPNQFFCESQRILNGGKDIKKEPIQPETPQPKPSVQKT
KDASSALASLNSSLEMDMEGLEDYFSEDS

Sequence of entity 5 (E), FASTA

>7OPL_5 Non-structural protein 1 (chains E)
GSMGHVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPY
VFIKRSDALSTNHGHKVVELVAEMDGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG

Ligands and cofactors

ID	Name	Formula	Copies
SF4	Iron/sulfur cluster	Fe4 S4	1
ZN	Zinc ion	Zn	3

Primary citation

Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with DNA polymerase alpha-primase. Kilkenny, M.L., Veale, C.E., Guppy, A. et al. Protein Sci (2022) 31:333-344. DOI 10.1002/pro.4220 · PubMed

Other PDB entries of the same protein (UniProt P09884 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4QCL 2.2 Å, Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex…
4Y97 2.51 Å, Crystal Structure of human Pol alpha B-subunit in complex with C-terminal domain of…
4Q5V 2.52 Å, Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex…
7N2M 2.9 Å, Crystal structure of DNA polymerase alpha catalytic core in complex with dCTP and…
6AS7 2.95 Å, Crystal structure of the catalytic core of human DNA polymerase alpha in ternary complex…
8VY3 2.98 Å, Human DNA polymerase alpha/primase - AavLEA1 (1:40 molar ratio)
8QJ7 3.07 Å, Cryo-EM structure of human DNA polymerase alpha-primase in pre-initiation stage 1
5IUD 3.3 Å, Human DNA polymerase alpha in binary complex with a DNA:DNA template-primer
8D96 3.35 Å, Human DNA polymerase alpha/primase elongation complex I bound to primer/template
9C8V 3.39 Å, Human DNA polymerase alpha/primase - CHAPSO (4 mM)
8B9D 3.4 Å, Human replisome bound by Pol Alpha
8D0B 3.43 Å, Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback…

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