9DNN: Insulin receptor

Insulin receptor in complex with both insulin and de novo designed site-2 binder "S2B". Determined by electron microscopy at 6.1 Å resolution. Released 1 Oct 2025.

Method: Electron microscopy
Resolution: 6.1 Å
Organisms: Mus musculus, Homo sapiens, synthetic construct
Chains: 6
Atoms: 15,074
Mol. weight: 350.67 kDa
Released: 1 Oct 2025

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

Secondary structure: helices and β-sheets

9DNN contains 58 α-helices and 150 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: 21 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	1
β-strand	12	1	2
α-helix	18-25	8
β-strand	26	1	1
β-strand	32-38	7	2
α-helix	44-47	4
β-strand	56-57	2	3
β-strand	60-66	7	2
β-strand	81-82	2	3
β-strand	88	1	4
β-strand	91	1	4
β-strand	93-96	4	2
β-strand	111-112	2	3
β-strand	117-120	4	2
β-strand	122	1	5
α-helix	133-136	4
β-strand	144-145	2	2
β-strand	148	1	5
α-helix	169-170	2
β-strand	171-173	3	6
β-strand	178-180	3	6
β-strand	182-184	3	7
β-strand	187-188	2	7
β-strand	201	1	8
β-strand	207	1	8
β-strand	212	1	9
β-strand	216	1	10
β-strand	225	1	10
β-strand	228	1	9
β-strand	231-232	2	11
β-strand	237-238	2	11
β-strand	246-248	3	12
β-strand	252-254	3	12
α-helix	256-267	12
β-strand	278-280	3	12
β-strand	283-285	3	12
β-strand	292-294	3	13
β-strand	300	1	12
β-strand	301-303	3	13
α-helix	304	1
α-helix	315-317	3
β-strand	318-321	4	14
α-helix	324-329	6
β-strand	335-336	2	15
β-strand	339-343	5	14
α-helix	351-357	7
β-strand	363-364	2	15
β-strand	368-371	4	14
β-strand	378	1	16
β-strand	388	1	17
β-strand	394	1	14
β-strand	398-403	6	14
β-strand	410	1	16
β-strand	421	1	17
β-strand	425-427	3	14
β-strand	428	1	18
β-strand	431	1	19
α-helix	436-446	11
β-strand	457	1	18
β-strand	462	1	19
β-strand	475-480	6	20
β-strand	485-489	5	20
α-helix	497-499	3
β-strand	500-509	10	21
β-strand	530-534	5	21
β-strand	553-555	3	20
α-helix	558-559	2
β-strand	563-572	10	21
β-strand	584	1	21
β-strand	588-591	4	21
α-helix	599-600	2
β-strand	601-607	7	22
β-strand	613-618	6	22
β-strand	629-630	2	23
β-strand	632-637	6	24
α-helix	642-645	4
α-helix	690-715	26
β-strand	761-762	2	24
β-strand	769-771	3	22
β-strand	780-785	6	24
β-strand	787-788	2	23
α-helix	799-800	2
β-strand	801-806	6	24
α-helix	807-810	4
α-helix	816-817	2
β-strand	820-824	5	25
β-strand	830-834	5	25
β-strand	844-853	10	26
β-strand	858-859	2	26
α-helix	865-871	7
β-strand	874-876	3	25
α-helix	879-880	2
β-strand	882-892	11	26
β-strand	896	1	26
α-helix	897-901	5
β-strand	905-907	3	26

Chain B: 21 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	27
β-strand	12	1	28
α-helix	18-25	8
β-strand	26	1	27
β-strand	32-38	7	28
α-helix	44-47	4
β-strand	56-57	2	29
β-strand	60-66	7	28
β-strand	81-82	2	29
β-strand	88	1	30
β-strand	91	1	30
β-strand	93-96	4	28
β-strand	111-112	2	29
β-strand	117-120	4	28
β-strand	122	1	31
α-helix	133-135	3
β-strand	144-145	2	28
β-strand	148	1	31
α-helix	169-170	2
β-strand	171-173	3	32
β-strand	178-180	3	32
β-strand	182-184	3	33
β-strand	187-188	2	33
β-strand	201	1	34
β-strand	207	1	34
β-strand	212	1	35
β-strand	216	1	36
β-strand	225	1	36
β-strand	228	1	35
β-strand	231-232	2	37
β-strand	237-238	2	37
β-strand	246-248	3	38
β-strand	252-254	3	38
α-helix	256-267	12
β-strand	278-280	3	38
β-strand	283-285	3	38
β-strand	292-294	3	39
β-strand	300	1	38
β-strand	301-303	3	39
α-helix	304	1
α-helix	315-317	3
β-strand	318-320	3	40
α-helix	324-329	6
β-strand	335-336	2	41
β-strand	339-342	4	40
α-helix	351-357	7
β-strand	363-364	2	41
β-strand	368-371	4	40
β-strand	378	1	42
β-strand	388	1	43
β-strand	394	1	40
β-strand	398-403	6	40
β-strand	410	1	42
β-strand	421	1	43
β-strand	425-427	3	40
β-strand	428	1	44
β-strand	431	1	45
α-helix	436-446	11
β-strand	457	1	44
β-strand	462	1	45
β-strand	475-480	6	46
β-strand	485-489	5	46
α-helix	497-499	3
β-strand	500-509	10	47
β-strand	530-534	5	47
β-strand	553-555	3	46
α-helix	558-559	2
β-strand	563-572	10	47
β-strand	584	1	47
β-strand	588-591	4	47
α-helix	599	1
β-strand	600-607	8	48
β-strand	613-620	8	48
β-strand	629-630	2	49
β-strand	632-637	6	50
α-helix	642-645	4
α-helix	690-715	26
β-strand	761-762	2	50
β-strand	769-771	3	48
β-strand	780-785	6	50
β-strand	787-788	2	49
α-helix	799-800	2
β-strand	801-806	6	50
α-helix	807-810	4
α-helix	816-817	2
β-strand	820-824	5	51
β-strand	830-834	5	51
β-strand	844-853	10	52
β-strand	858-859	2	52
α-helix	865-871	7
β-strand	874-876	3	51
α-helix	879-880	2
β-strand	882-892	11	52
β-strand	896	1	52
α-helix	897-901	5
β-strand	905-907	3	52

Chains C and D: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	8-18	11
α-helix	57	1
α-helix	58-63	6
α-helix	69-72	4

Chains E and F: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	2-14	13
α-helix	19-32	14
α-helix	37-51	15
α-helix	54-63	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1372	Mus musculus	P15208 (AlphaFold model)
Insulin	C, D	protein	110	Homo sapiens	P01308 (AlphaFold model)
Designed site-2 binder S2B	E, F	protein	65	synthetic construct

Sequence of entity 1 (A, B), FASTA

>9DNN_1 Insulin receptor (chains A, B)
MGFGRGCETTAVPLLVAVAALLVGTAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHL
QILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYAL
VIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNE
ECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECL
GNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPG
CHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGC
TVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETL
EIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQE
RNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQ
NVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVT
FSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVY
WERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQ
ILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPT
SQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKA
DDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERG
CRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSV
VIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELG
QGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLL
GVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYL
NAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKD
GVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMR
MCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLD
RSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS

Sequence of entity 2 (C, D), FASTA

>9DNN_2 Insulin (chains C, D)
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN

Sequence of entity 3 (E, F), FASTA

>9DNN_3 Designed site-2 binder S2B (chains E, F)
SKLEEIEELLKELSKTNPLAKDILWVIEVRTEDGHDPKSELVFIRQYLKTLNTPEAREIL
KIVAP

Primary citation

Tuning insulin receptor signaling using de novo-designed agonists. Wang, X., Cardoso, S., Cai, K. et al. Mol Cell (2025) 85:4064. DOI 10.1016/j.molcel.2025.09.020 · PubMed

Other PDB entries of the same protein (UniProt P15208 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1LK2 1.35 Å, 1.35A crystal structure of H-2Kb complexed with the GNYSFYAL peptide
7SL7 3.1 Å, Full-length insulin receptor bound with both site 1 binding deficient mutant insulin…
7SL1 3.4 Å, Full-length insulin receptor bound with site 1 binding deficient mutant insulin (A-V3E)
7SL3 3.4 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R)…
7STH 3.5 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound)…
8DTM 3.5 Å, Cryo-EM structure of insulin receptor (IR) bound with S597 component 2
7SL2 3.6 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R)…
7SL6 3.7 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R)…
8EZ0 3.7 Å, Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically…
7STK 4.0 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound)…
7STJ 4.4 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound)…
8EYX 4.5 Å, Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically…

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