9KMC: Heterotrimeric interleukin-2 receptor

Cryo-EM structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2 and anti-CD25 Fab S417. Determined by electron microscopy at 2.97 Å resolution. Released 19 Nov 2025.

Method: Electron microscopy
Resolution: 2.97 Å
Organisms: Homo sapiens, synthetic construct
Chains: 6
Atoms: 8,935
Mol. weight: 146.78 kDa
Ligands: NAG
Released: 19 Nov 2025

Explore 9KMC in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9KMC contains 30 α-helices and 108 β-strands across 6 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: 4 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	23	1	1
β-strand	34-37	4	2
β-strand	41-42	2	3
β-strand	46-48	3	4
β-strand	51	1	5
β-strand	55-57	3	6
α-helix	58	1
β-strand	64-66	3	4
β-strand	67-70	4	7
β-strand	73-76	4	7
β-strand	82-84	3	6
β-strand	121	1	3
β-strand	124-125	2	3
α-helix	127-130	4
β-strand	134	1	5
β-strand	140-141	2	4
β-strand	143	1	1
β-strand	147-152	6	2
α-helix	153	1
β-strand	157-158	2	8
β-strand	165-167	3	2
β-strand	168	1	9
β-strand	171	1	10
β-strand	174	1	10
β-strand	177	1	9
α-helix	178-180	3
β-strand	184-185	2	8

Chain B: 5 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	32-38	7	11
β-strand	43-50	8	11
α-helix	53-54	2
β-strand	59-65	7	12
β-strand	72-75	4	12
β-strand	77-80	4	11
β-strand	83-89	7	11
β-strand	104-112	9	12
β-strand	115-124	10	12
β-strand	130	1	11
α-helix	132-135	4
β-strand	136-143	8	13
β-strand	148-153	6	13
β-strand	165-172	8	14
α-helix	182-183	2
β-strand	184-186	3	14
β-strand	192-195	4	13
β-strand	203-212	10	14
α-helix	220-226	7
β-strand	227-230	4	14
α-helix	231-233	3

Chain C: 3 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	55-59	5
β-strand	60-65	6	15
β-strand	70-74	5	15
β-strand	86-92	7	16
β-strand	100-101	2	16
β-strand	105-108	4	15
β-strand	111-117	7	15
β-strand	127-133	7	16
β-strand	141-147	7	16
α-helix	148-150	3
β-strand	152-153	2	15
α-helix	155-157	3
β-strand	158-166	9	17
β-strand	169-175	7	17
β-strand	184-189	6	18
β-strand	190-191	2	19
β-strand	198-202	5	18
β-strand	207-211	5	17
β-strand	218-221	4	19
β-strand	223-226	4	18
β-strand	244-247	4	19

Chain D: 7 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	22-24	3
α-helix	28-48	21
α-helix	56-59	4
β-strand	64-67	4	20
α-helix	73-76	4
α-helix	77-93	17
α-helix	102-117	16
β-strand	127-132	6	20
α-helix	134-152	19

Chain E: 6 helices, 27 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	21
β-strand	10-12	3	22
β-strand	18-25	8	21
α-helix	29-31	3
β-strand	34-39	6	22
β-strand	45-52	8	22
β-strand	57-60	4	22
β-strand	65	1	21
β-strand	68-73	6	21
β-strand	78-83	6	21
α-helix	88-90	3
β-strand	92-100	9	22
β-strand	105-109	5	22
β-strand	113-117	5	22
β-strand	123	1	23
α-helix	124-125	2
β-strand	126-130	5	24
α-helix	134-136	3
β-strand	138	1	24
β-strand	141-151	11	24
β-strand	152	1	23
β-strand	157-158	2	25
β-strand	160	1	26
β-strand	165	1	26
β-strand	171	1	24
α-helix	172-174	3
β-strand	175-176	2	24
β-strand	182-191	10	24
α-helix	193-196	4
β-strand	200-201	2	27
β-strand	204-206	3	25
β-strand	211-213	3	25
β-strand	216-217	2	27

Chain F: 5 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	28
β-strand	10-13	4	29
β-strand	19-25	7	28
β-strand	33-37	5	29
β-strand	44-48	5	29
β-strand	52-53	2	29
α-helix	54	1
β-strand	61-66	6	28
β-strand	69-74	6	28
α-helix	79-81	3
β-strand	84-89	6	29
α-helix	95	1
β-strand	96-97	2	29
β-strand	101-105	5	29
β-strand	110	1	30
β-strand	113-117	5	31
α-helix	118-120	3
β-strand	125	1	31
β-strand	128-138	11	31
β-strand	139	1	30
β-strand	143-149	7	32
β-strand	153	1	32
β-strand	158-162	5	31
β-strand	172-181	10	31
α-helix	182-187	6
β-strand	190-197	8	32
β-strand	204-209	6	32

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Interleukin-2 receptor subunit alpha	A	protein	240	Homo sapiens	P01589 (AlphaFold model)
Interleukin-2 receptor subunit beta	B	protein	222	Homo sapiens	P14784 (AlphaFold model)
Cytokine receptor common subunit gamma	C	protein	241	Homo sapiens	P31785 (AlphaFold model)
Interleukin-2	D	protein	133	Homo sapiens	P60568 (AlphaFold model)
Fab S417 heavy chain	E	protein	228	synthetic construct
Fab S417 light chain	F	protein	213	synthetic construct

Sequence of entity 1 (A), FASTA

>9KMC_1 Interleukin-2 receptor subunit alpha (chains A)
ELCDDDPPEIPHATFKAMAYKEGTMLNCECKRGFRRIKSGSLYMLCTGNSSHSSWDNQCQ
CTSSATRNTTKQVTPQPEEQKERKTTEMQSPMQPVDQASLPGHCREPPPWENEATERIYH
FVVGQMVYYQCVQGYRALHRGPAESVCKMTHGKTRWTQPQLICTGEMETSQFPGEEKPQA
SPEGRPESETSCLVTTTDFQIQTEMAATMETSIFTTEYQGGGGSGGGGSGGGGSHHHHHH

Sequence of entity 2 (B), FASTA

>9KMC_2 Interleukin-2 receptor subunit beta (chains B)
AVNGTSQFTCFYNSRANISCVWSQDGALQDTSCQVHAWPDRRRWNQTCELLPVSQASWAC
NLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMAIQDFKPFENLRLMAPISLQVVHVETH
RCNISWEISQASHYFERHLEFEARTLSPGHTWEEAPLLTLKQKQEWICLETLTPDTQYEF
QVRVKPLQGEFTTWSPWSQPLAFRTKPAALGKDTHHHHHHHH

Sequence of entity 3 (C), FASTA

>9KMC_3 Cytokine receptor common subunit gamma (chains C)
LNTTILTPNGNEDTTADFFLTTMPTDSLSVSTLPLPEVQCFVFNVEYMNCTWQSSSEPQP
TNLTLHYWYKNSDNDKVQKCSHYLFSEEITSGCQLQKKEIHLYQTFVVQLQDPREPRRQA
TQMLKLQNLVIPWAPENLTLHKLSESQLELNWNNRFLNHCLEHLVQYRTDWDHSWTEQSV
DYRHKFSLPSVDGQKRYTFRVRSRFNPLCGSAQHWSEWSHPIHWGSNTSKENPHHHHHHH
H

Sequence of entity 4 (D), FASTA

>9KMC_4 Interleukin-2 (chains D)
APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE
EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR
WITFCQSIISTLT

Sequence of entity 5 (E), FASTA

>9KMC_5 Fab S417 heavy chain (chains E)
QVQLHQSGDDLVKPGASVKLSCRASGYTFTSYWINWVKQRPGQGLEWIGRILPGTNSIYY
SEIFKGKASLTVDTSSNTAYIQLSSLSSEDSAVYFCARLLWNKGAMDYWGQGTSVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCENLYFQ

Sequence of entity 6 (F), FASTA

>9KMC_6 Fab S417 light chain (chains F)
QIVLSQSPVILSASPGEKVTMTCRASSGVSSIHWYQQQPGSSPKPWIYDTSSLASGVPAR
FSGSGSGTSYSLTISRVEAEDAATYYCQQWSSNPPTFGAGTKLELKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Ligands and cofactors

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

Primary citation

CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting. Itoh-Nakadai, A., Liang, M., Shindo, M. et al. Nat Commun (2026) 17:101-101. DOI 10.1038/s41467-025-67745-x · PubMed

Other PDB entries of the same protein (UniProt P01589 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6YIO 1.83 Å, Crystal structure of FAB RG6292 in complex with CD25 ecd
2B5I 2.3 Å, cytokine receptor complex
1Z92 2.8 Å, structure of interleukin-2 with its alpha receptor
3NFP 2.86 Å, Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with…
3IU3 2.9 Å, Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex…
2ERJ 3.0 Å, Crystal structure of the heterotrimeric interleukin-2 receptor in complex with…
7F9W 3.2 Å, CD25 in complex with Fab
7ZMZ 3.2 Å, Engineered Interleukin 2 bound to CD25 receptor
6VWU 3.4 Å, X-ray structure of ALKS 4230, a fusion of circularly permuted human Interleukin-2 and…

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