8IOW: Sarilumab Fab/IL-6R complex

Cryo-EM structure of the sarilumab Fab/IL-6R complex. Determined by electron microscopy at 3.2 Å resolution. Released 20 Mar 2024.

Method: Electron microscopy
Resolution: 3.2 Å
Organism: Homo sapiens
Chains: 4
Atoms: 4,178
Mol. weight: 128.09 kDa
Ligands: NAG
Released: 20 Mar 2024

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

Secondary structure: helices and β-sheets

8IOW contains 12 α-helices and 54 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 D2: 0 helices, 1 β-strand

Element	Residues	Length	Sheet
β-strand	123	1	1

Chain H: 5 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	12
β-strand	11-12	2	13
β-strand	19	1	14
β-strand	21-25	5	12
β-strand	34-39	6	15
β-strand	45-51	7	15
β-strand	58-60	3	15
β-strand	69-73	5	14
β-strand	78-82	5	14
α-helix	88-90	3
β-strand	92-98	7	15
β-strand	106	1	15
β-strand	111-112	2	15
β-strand	113-114	2	13
β-strand	123-127	5	16
β-strand	139-148	10	16
β-strand	153-157	5	17
β-strand	166-168	3	16
α-helix	169-171	3
β-strand	172-173	2	16
β-strand	179-187	9	16
α-helix	189-191	3
α-helix	196	1
β-strand	197-203	7	17
α-helix	204-206	3
β-strand	208-214	7	17

Chain I: 3 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	214	1	1
α-helix	216-219	4
β-strand	223-225	3	2
β-strand	235-237	3	2
β-strand	251-253	3	3
β-strand	254-257	4	4
β-strand	266-269	4	4
α-helix	270-271	2
β-strand	276-278	3	2
β-strand	289-290	2	5
β-strand	294-296	3	3
α-helix	303-309	7
β-strand	310-311	2	5

Chain L: 4 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	4-6	3	6
β-strand	10-13	4	7
β-strand	19-25	7	6
β-strand	33-38	6	7
β-strand	45-46	2	7
β-strand	48-49	2	8
β-strand	53-54	2	8
β-strand	62-67	6	6
β-strand	70-75	6	6
α-helix	80-82	3
β-strand	85-90	6	7
β-strand	98	1	7
β-strand	103-106	4	7
β-strand	111	1	9
β-strand	114-118	5	10
α-helix	119-121	3
α-helix	122-127	6
β-strand	129-139	11	10
β-strand	140	1	9
β-strand	145-150	6	11
β-strand	154-155	2	11
β-strand	159-163	5	10
β-strand	173-182	10	10
α-helix	183-188	6
β-strand	192-197	6	11
β-strand	205-209	5	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Interleukin-6 receptor subunit alpha	D2, I	protein	365	Homo sapiens	P08887 (AlphaFold model)
Light chain of Sarilumab Fab	L	protein	214	Homo sapiens
Heavy chain of Sarilumab Fab	H	protein	223	Homo sapiens

Sequence of entity 1 (D2, I), FASTA

>8IOW_1 Interleukin-6 receptor subunit alpha (chains D2, I)
MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHW
VLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLS
CFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV
PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQD
PHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQ
GEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPGSRRR
GSCGL

Sequence of entity 2 (L), FASTA

>8IOW_2 Light chain of Sarilumab Fab (chains L)
DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLESGVPS
RFSGSGSGTDFTLTISSLQPEDFASYYCQQANSFPYTFGQGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Sequence of entity 3 (H), FASTA

>8IOW_3 Heavy chain of Sarilumab Fab (chains H)
EVQLVESGGGLVQPGRSLRLSCAASRFTFDDYAMHWVRQAPGKGLEWVSGISWNSGRIGY
ADSVKGRFTISRDNAENSLFLQMNGLRAEDTALYYCAKGRDSFDIWGQGTMVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH

Ligands and cofactors

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

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).
8D82 3.22 Å, Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full…
8J6F 3.3 Å, Cryo-EM structure of the Tocilizumab Fab/IL-6R complex
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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