8K4Q: Nanobody HuNb103

Crystal structure of nanobody HuNb103 bound to human interleukin-4 receptor subunit alpha. Determined by X-ray diffraction at 2.59 Å resolution. Released 26 Jun 2024.

Method: X-ray diffraction
Resolution: 2.59 Å
Organisms: Homo sapiens, Camelus dromedarius
Chains: 4
Atoms: 5,304
Mol. weight: 78.23 kDa
Ligands: NAG
Released: 26 Jun 2024

Explore 8K4Q in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8K4Q contains 19 α-helices and 56 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: 5 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	5-11	7	1
β-strand	16-22	7	1
β-strand	33-39	7	2
β-strand	47-49	3	2
β-strand	52-55	4	1
β-strand	58-64	7	1
β-strand	74-80	7	2
β-strand	83-90	8	2
α-helix	92-94	3
β-strand	96	1	1
α-helix	98-101	4
β-strand	102-107	6	3
β-strand	113-119	7	3
α-helix	128-130	3
β-strand	133-140	8	4
β-strand	143-152	10	4
β-strand	158-162	5	3
α-helix	163-165	3
β-strand	171-179	9	4
β-strand	185	1	1
α-helix	187-193	7
β-strand	194-197	4	4

Chain B: 4 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	5
β-strand	10-12	3	6
β-strand	18-24	7	5
α-helix	28-30	3
β-strand	33-39	7	6
β-strand	46-51	6	6
β-strand	58-60	3	6
α-helix	62-64	3
β-strand	68-73	6	5
α-helix	74-76	3
β-strand	78-83	6	5
α-helix	88-90	3
β-strand	92-99	8	6
β-strand	108-109	2	6
β-strand	113-117	5	6

Chain C: 6 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	5-11	7	7
β-strand	16-22	7	7
α-helix	29-32	4
β-strand	33-39	7	8
β-strand	47-49	3	8
β-strand	52-53	2	7
β-strand	58-64	7	7
β-strand	74-80	7	8
β-strand	83-90	8	8
α-helix	92-94	3
β-strand	96	1	7
α-helix	98-101	4
β-strand	102-107	6	9
β-strand	113-119	7	9
α-helix	128-130	3
β-strand	132-140	9	10
β-strand	143-152	10	10
β-strand	158-162	5	9
α-helix	163-165	3
β-strand	171-180	10	10
β-strand	185	1	7
α-helix	187-193	7
β-strand	194-197	4	10

Chain D: 4 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	11
β-strand	10-12	3	12
β-strand	18-24	7	11
α-helix	28-30	3
β-strand	33-38	6	12
β-strand	46-51	6	12
β-strand	58-60	3	12
α-helix	62-64	3
β-strand	68-73	6	11
α-helix	74-76	3
β-strand	78-83	6	11
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	108-109	2	12
β-strand	113-117	5	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Interleukin-4 receptor subunit alpha	A, C	protein	214	Homo sapiens	P24394 (AlphaFold model)
IL-4R nanobody HuNb103	B, D	protein	121	Camelus dromedarius

Sequence of entity 1 (A, C), FASTA

>8K4Q_1 Interleukin-4 receptor subunit alpha (chains A, C)
MKVLQEPTCVSDYMSISTCEWKMNGPTNCSTELRLLYQLVFLLSEAHTCIPENNGGAGCV
CHLLMDDVVSADNYTLDLWAGQQLLWKGSFKPSEHVKPRAPGNLTVHTNVSDTLLLTWSN
PYPPDNYLYNHLTYAVNIWSENDPADFRIYNVTYLEPSLRIAASTLKSGISYRARVRAWA
QCYNTTWSEWSPSTKWHNSYREPFEQHENLYFQG

Sequence of entity 2 (B, D), FASTA

>8K4Q_2 IL-4R nanobody HuNb103 (chains B, D)
GSEVQLQESGGGLVQPGGSLRLSCAASGSTSYRYCMAWFRQAPGKGLEAVASIRPRSGRA
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAMYYCAASDNDGNCQDYWGKGTLVTVS
S

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	4

Primary citation

A novel inhalable nanobody targeting IL-4R alpha for the treatment of asthma. Zhu, M., Ma, L., Zhong, P. et al. J Allergy Clin Immunol (2024) 154:1008-1021. DOI 10.1016/j.jaci.2024.05.027 · PubMed

Other PDB entries of the same protein (UniProt P24394 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1IAR 2.3 Å, Interleukin-4 / receptor alpha chain complex
6WGL 2.82 Å, Dupilumab fab with Crystal Kappa design complexed with human IL-4 receptor
3BPL 2.93 Å, Crystal structure of the IL4-IL4R-Common Gamma ternary complex
3BPO 3.0 Å, Crystal structure of the IL13-IL4R-IL13Ra ternary complex
5E4E 3.0 Å, Engineered Interleukin-13 bound to receptor
3BPN 3.02 Å, Crystal structure of the IL4-IL4R-IL13Ra ternary complex
6OEL 3.1 Å, Engineered Fab bound to IL-4 receptor
8Z8L 3.96 Å, structure of IL-4Ra in complex with an nanobody 4E9
1IRS Irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, NMR, minimized average…

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