7B2Q: Complement C4b

Cryo-EM structure of complement C4b in complex with nanobody B12. Determined by electron microscopy at 3.76 Å resolution. Released 2 Mar 2022.

Method: Electron microscopy
Resolution: 3.76 Å
Organisms: Homo sapiens, Lama glama
Chains: 4
Atoms: 11,611
Mol. weight: 205.51 kDa
Ligands: NAG
Released: 2 Mar 2022

Explore 7B2Q in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7B2Q contains 37 α-helices and 123 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: 13 helices, 63 β-strands

Element	Residues	Length	Sheet
β-strand	22-28	7	1
β-strand	30-32	3	2
β-strand	37-44	8	1
β-strand	51-52	2	3
β-strand	55-59	5	2
α-helix	61-63	3
β-strand	67	1	2
β-strand	72-73	2	2
β-strand	76-77	2	3
β-strand	82-87	6	1
α-helix	91-96	6
β-strand	107-113	7	2
α-helix	116-119	4
β-strand	127-135	9	2
β-strand	140-145	6	4
β-strand	149-150	2	5
β-strand	155-163	9	4
β-strand	169	1	4
β-strand	173-179	7	6
β-strand	185-192	8	6
β-strand	197-203	7	4
α-helix	208-209	2
β-strand	211-212	2	5
β-strand	214-219	6	6
β-strand	227-229	3	6
β-strand	232-233	2	5
β-strand	241-247	7	7
β-strand	251-253	3	8
β-strand	262-270	9	7
β-strand	275	1	7
β-strand	279-280	2	9
β-strand	282-287	6	8
β-strand	293-295	3	8
β-strand	303-304	2	9
β-strand	306	1	7
β-strand	309-314	6	7
α-helix	316-326	11
β-strand	337-342	6	8
β-strand	345	1	9
β-strand	352	1	9
β-strand	355-356	2	8
β-strand	361-363	3	8
β-strand	367-370	4	10
β-strand	384-392	9	10
β-strand	397	1	10
β-strand	403-410	8	11
α-helix	415-416	2
β-strand	417-423	7	11
β-strand	430-435	6	10
β-strand	443-450	8	11
β-strand	456-463	8	11
α-helix	464-466	3
β-strand	473	1	12
β-strand	476	1	13
α-helix	482-484	3
β-strand	488-493	6	13
β-strand	495	1	12
β-strand	504-510	7	14
β-strand	515-522	8	14
β-strand	527-532	6	13
β-strand	540-541	2	15
β-strand	542-549	8	14
β-strand	552-555	4	14
β-strand	560-561	2	15
β-strand	572-574	3	16
α-helix	581-582	2
β-strand	586-592	7	16
β-strand	597-599	3	17
β-strand	602	1	18
β-strand	605	1	19
α-helix	607-610	4
α-helix	621-629	9
α-helix	643-649	7
β-strand	652-655	4	1
β-strand	660	1	1
α-helix	661-664	4

Chain B: 20 helices, 35 β-strands

Element	Residues	Length	Sheet
β-strand	775	1	20
β-strand	787-788	2	17
β-strand	794-798	5	16
β-strand	804-808	5	19
β-strand	809	1	18
β-strand	811-814	4	17
β-strand	820-821	2	17
α-helix	822-824	3
β-strand	825-829	5	19
β-strand	833-836	4	21
β-strand	843	1	22
β-strand	851	1	23
β-strand	854-857	4	21
β-strand	863-869	7	20
α-helix	870-871	2
β-strand	875-876	2	24
β-strand	885-889	5	20
β-strand	893-894	2	21
β-strand	899	1	23
β-strand	902-903	2	24
β-strand	908-916	9	20
α-helix	917-918	2
β-strand	925-932	8	20
β-strand	933	1	22
α-helix	934-935	2
β-strand	939-945	7	6
β-strand	959-960	2	25
α-helix	961-963	3
β-strand	975-981	7	6
α-helix	1000-1003	4
α-helix	1013-1016	4
α-helix	1019-1031	13
α-helix	1039-1057	19
α-helix	1073-1074	2
α-helix	1076-1089	14
α-helix	1097-1109	13
β-strand	1111	1	26
β-strand	1117	1	26
α-helix	1126-1129	4
α-helix	1138-1155	18
α-helix	1162-1185	24
α-helix	1190-1202	13
α-helix	1207-1220	14
α-helix	1259-1274	16
α-helix	1282-1293	12
α-helix	1303-1319	17
β-strand	1329-1335	7	25
β-strand	1338-1344	7	25
β-strand	1356	1	6
β-strand	1359	1	6
β-strand	1366-1368	3	25
β-strand	1377-1385	9	6
β-strand	1397-1401	5	27
β-strand	1404-1405	2	28
β-strand	1409	1	29

Chain C: 2 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	1466-1468	3	28
β-strand	1470-1474	5	27
β-strand	1484-1486	3	30
β-strand	1489	1	30
β-strand	1494-1496	3	28
α-helix	1498-1506	9
β-strand	1512-1518	7	30
β-strand	1521-1526	6	30
β-strand	1538-1542	5	28
α-helix	1545	1
β-strand	1546	1	29
β-strand	1553-1555	3	31
β-strand	1556-1558	3	30
β-strand	1567-1569	3	31
β-strand	1581	1	32
β-strand	1590	1	32

Chain D: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	33
β-strand	13	1	34
β-strand	19-24	6	33
β-strand	31-35	5	35
β-strand	42-47	6	35
β-strand	54-56	3	35
α-helix	58-60	3
β-strand	65-69	5	33
β-strand	74-78	5	33
α-helix	84-86	3
β-strand	88-93	6	35
β-strand	114-116	3	35
β-strand	119	1	34

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Complement C4 beta chain	A	protein	656	Homo sapiens	P0C0L4 (AlphaFold model)
Complement C4 alpha chain	B	protein	767	Homo sapiens	P0C0L4 (AlphaFold model)
Complement C4 gamma chain	C	protein	291	Homo sapiens	P0C0L4 (AlphaFold model)
Anti-C4b nanobody B12	D	protein	139	Lama glama

Sequence of entity 1 (A), FASTA

>7B2Q_1 Complement C4 beta chain (chains A)
KPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLRNPSRNNVPCSPKVDFTLSSE
RDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRG
HLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQ
DDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKPYILTVPGHL
DEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLESQTKLVNGQSHISLSKAEF
QDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAELTSWYFVSSPFSLDLSKTKRHLV
PGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQ
TISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSG
ATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHGDHPVANSLR
VDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVALGALDTALYAAGSKSHKPL
NMGKVFEAMNSYDLGCGPGGGDSALQVFQAAGLAFSDGDQWTLSRKRLSCPKEKTT

Sequence of entity 2 (B), FASTA

>7B2Q_2 Complement C4 alpha chain (chains B)
NVNFQKAINEKLGQYASPTAKRCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFA
ESLRKKSRDKGQAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWL
PDSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLELRPVLYNYL
DKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSF
EFPVGDAVSKVLQIEKEGAIHREELVYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVR
VTASDPLDTLGSEGALSPGGVASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPP
ETKDHAVDLIQKGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEK
LQETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDE
GAEPLKQRVEASISKANSFLGEKASAGLLGAHAAAITAYALSLTKAPVDLLGVAHNNLMA
MAQETGDNLYWGSVTGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKA
EMADQASAWLTRQGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGF
KSHALQLNNRQIRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQI
EVTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEG

Sequence of entity 3 (C), FASTA

>7B2Q_3 Complement C4 gamma chain (chains C)
EAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVS
HFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAP
SKSRLLATLCSAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLR
EDSRAAFRLFETKITQVLHFTKDVKAAANQMRNFLVRASCRLRLEPGKEYLIMGLDGATY
DLEGHPQYLLDSNSWIEEMPSERLCRSTRQRAACAQLNDFLQEYGTQGCQV

Sequence of entity 4 (D), FASTA

>7B2Q_4 Anti-C4b nanobody B12 (chains D)
EVQLVESGGGLVQAGGSLRLSCVASERTYMAWFRQAPGKEREFVAAITSSGMMTEYAPSV
KGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAADLRQRFGERVTEYDYWGQGTQVTVSS
HGSGLVPRGSGGGHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	3

Primary citation

Multifaceted Activities of Seven Nanobodies against Complement C4b. De la O Becerra, K.I., Oosterheert, W., van den Bos, R.M. et al. J Immunol (2022) 208:2207-2219. DOI 10.4049/jimmunol.2100647 · PubMed

Other PDB entries of the same protein (UniProt P0C0L4 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1HZF 2.3 Å, C4ADG fragment of human complement factor C4A
6YSQ 3.3 Å, The hC4Nb8 complement inhibitory nanobody in complex with C4b
7B2M 3.39 Å, Cryo-EM structure of complement C4b in complex with nanobody E3
7B2P 3.43 Å, Cryo-EM structure of complement C4b in complex with nanobody B5
5JTW 3.5 Å, Crystal structure of complement C4b re-refined using iMDFF
9QJ5 3.5 Å, Structure of the Complement classical and lectin pathway proconvertase, C4b2
9QK2 3.5 Å, Structure of the Complement classical and lectin pathway C3 convertase in complex with…
5JPN 3.6 Å, Structure of human complement C4 rebuilt using iMDFF
5JPM 3.75 Å, Structure of the complex of human complement C4 with MASP-2 rebuilt using iMDFF
9QJ4 3.9 Å, Structure of the Complement classical and lectin pathway proconvertase, C4b2
9QPY 4.3 Å, Structure of the Complement classical and lectin pathway C3 convertase

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