8J6F: Tocilizumab Fab/IL-6R complex

Cryo-EM structure of the Tocilizumab Fab/IL-6R complex. Determined by electron microscopy at 3.3 Å resolution. Released 27 Mar 2024.

Method: Electron microscopy
Resolution: 3.3 Å
Organism: Homo sapiens
Chains: 4
Atoms: 3,870
Mol. weight: 89.31 kDa
Ligands: NAG
Released: 27 Mar 2024

Explore 8J6F in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8J6F contains 11 α-helices and 49 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 B: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	110-111	2

Chain H: 6 helices, 19 β-strands

Element	Residues	Length	Sheet
β-strand	4-5	2	1
α-helix	12-13	2
β-strand	18-24	7	1
β-strand	35-40	6	2
β-strand	47-52	6	2
β-strand	58-59	2	2
β-strand	68	1	1
α-helix	74-76	3
β-strand	78-83	6	1
β-strand	92-96	5	2
β-strand	99	1	3
β-strand	106	1	3
β-strand	114-115	2	2
α-helix	123-125	3
β-strand	126-130	5	4
β-strand	143-151	9	4
β-strand	159-160	2	5
β-strand	169-171	3	4
α-helix	172-174	3
β-strand	175-176	2	4
β-strand	182-189	8	4
α-helix	192-194	3
α-helix	199	1
β-strand	200-206	7	5
β-strand	211-217	7	5

Chain I: 2 helices, 5 β-strands

Element	Residues	Length	Sheet
α-helix	216-219	4
β-strand	220-223	4	13
β-strand	237-239	3	13
β-strand	251-258	8	14
β-strand	268-269	2	14
β-strand	289-296	8	14
α-helix	303-307	5

Chain L: 2 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	5-7	3	6
β-strand	10-13	4	7
β-strand	19-24	6	6
β-strand	33-37	5	8
α-helix	43-44	2
β-strand	45-49	5	8
β-strand	53-54	2	8
α-helix	55	1
β-strand	62-67	6	6
β-strand	70-75	6	6
β-strand	86	1	9
β-strand	87-90	4	8
β-strand	97	1	2
β-strand	98	1	8
β-strand	102	1	9
β-strand	103-106	4	7
β-strand	111	1	10
β-strand	114-115	2	11
β-strand	118	1	11
β-strand	130-137	8	11
β-strand	140	1	10
β-strand	144-148	5	12
β-strand	160	1	11
β-strand	163	1	11
β-strand	174-181	8	11
β-strand	193-198	6	12
β-strand	205-208	4	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Heavy chain of Tocilizumab Fab	H	protein	226	Homo sapiens
Light chain of Tocilizumab Fab	L	protein	214	Homo sapiens
Interleukin-6 receptor subunit alpha	I	protein	365	Homo sapiens	P08887 (AlphaFold model)
IL6R-D2 peptide	B	protein	10	Homo sapiens	P08887 (AlphaFold model)

Sequence of entity 1 (H), FASTA

>8J6F_1 Heavy chain of Tocilizumab Fab (chains H)
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTY
NPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH

Sequence of entity 2 (L), FASTA

>8J6F_2 Light chain of Tocilizumab Fab (chains L)
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS
RFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Sequence of entity 3 (I), FASTA

>8J6F_3 Interleukin-6 receptor subunit alpha (chains I)
MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHW
VLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLS
CFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV
PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQD
PHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQ
GEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPGSRRR
GSCGL

Sequence of entity 4 (B), FASTA

>8J6F_4 IL6R-D2 peptide (chains B)
FRKSPLSNVV

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1

Primary citation

Structural insights into IL-6 signaling inhibition by therapeutic antibodies. Wang, M., Chen, L., He, J. et al. Cell Rep (2024) 43:113819-113819. DOI 10.1016/j.celrep.2024.113819 · PubMed

Other PDB entries of the same protein (UniProt P08887 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1N26 2.4 Å, Crystal Structure of the extra-cellular domains of Human Interleukin-6 Receptor alpha…
5FUC 2.7 Å, Biophysical and cellular characterisation of a junctional epitope antibody that locks…
7DC8 2.76 Å, Crystal structure of Switch Ab Fab and hIL6R in complex with ATP
8QY5 3.1 Å, Structure of interleukin 6.
8QY6 3.16 Å, Structure of interleukin 6 (gp130 P496L mutant).
8IOW 3.2 Å, Cryo-EM structure of the sarilumab Fab/IL-6R complex
8D82 3.22 Å, Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full…
1P9M 3.65 Å, Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex
2ARW The solution structure of the membrane proximal cytokine receptor domain of the human…

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