8EYY: Insulin receptor

Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically decoupled alpha CTs (C684S/C685S/C687S, denoted as IR-3CS) Asymmetric conformation 2. Determined by electron microscopy at 4.9 Å resolution. Released 9 Nov 2022.

Method: Electron microscopy
Resolution: 4.9 Å
Organisms: Mus musculus, Homo sapiens
Chains: 6
Atoms: 14,301
Mol. weight: 354.33 kDa
Released: 9 Nov 2022

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

Secondary structure: helices and β-sheets

8EYY contains 61 α-helices and 149 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: 22 helices, 70 β-strands

Element	Residues	Length	Sheet
β-strand	9-14	6	1
α-helix	19-23	5
β-strand	28-29	2	2
β-strand	30-38	9	1
α-helix	44-47	4
β-strand	56-57	2	2
β-strand	61-66	6	1
β-strand	81-82	2	2
β-strand	88	1	1
β-strand	91-98	8	1
β-strand	111-112	2	2
β-strand	116-120	5	1
β-strand	122	1	3
α-helix	133-136	4
β-strand	137	1	2
β-strand	144-145	2	1
β-strand	148	1	3
β-strand	212	1	4
β-strand	213	1	5
β-strand	215	1	5
β-strand	216	1	6
β-strand	225	1	6
β-strand	228	1	4
β-strand	231-233	3	7
β-strand	236-238	3	7
β-strand	246-248	3	7
β-strand	252-254	3	7
α-helix	256-265	10
β-strand	278-280	3	8
β-strand	283-285	3	8
β-strand	292-295	4	8
β-strand	300-303	4	8
α-helix	308-309	2
β-strand	311-312	2	9
α-helix	315-317	3
β-strand	318-321	4	10
α-helix	324-329	6
β-strand	335-336	2	9
β-strand	339-342	4	10
α-helix	353-358	6
β-strand	363-364	2	9
β-strand	368-371	4	10
β-strand	378	1	11
β-strand	387-388	2	9
β-strand	394	1	10
β-strand	398-403	6	10
β-strand	410	1	11
β-strand	420-421	2	9
β-strand	425-426	2	10
β-strand	428	1	12
β-strand	429	1	10
β-strand	431	1	13
α-helix	436-445	10
β-strand	457	1	12
β-strand	462	1	13
β-strand	471-472	2	14
β-strand	475-479	5	15
β-strand	486-489	4	15
α-helix	490-492	3
α-helix	497-499	3
β-strand	500-509	10	14
α-helix	535-537	3
β-strand	552-554	3	15
α-helix	558-559	2
β-strand	563-572	10	14
β-strand	583-584	2	14
β-strand	588-591	4	14
α-helix	592-594	3
α-helix	599-600	2
β-strand	601-607	7	16
β-strand	613-618	6	16
β-strand	629-636	8	17
α-helix	638-640	3
α-helix	642-644	3
α-helix	691-715	25
β-strand	761-764	4	17
β-strand	769-772	4	16
β-strand	780-790	11	17
β-strand	796-797	2	17
β-strand	801-806	6	17
α-helix	807-809	3
α-helix	816	1
β-strand	817-824	8	18
β-strand	830-835	6	18
β-strand	844-853	10	19
β-strand	859-864	6	19
α-helix	865-871	7
β-strand	874-876	3	18
β-strand	882-892	11	19
β-strand	896-899	4	19
α-helix	900-901	2
β-strand	903-907	5	19

Chain B: 23 helices, 73 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	20
β-strand	9	1	21
β-strand	12-14	3	22
α-helix	19-23	5
β-strand	26	1	20
β-strand	28-29	2	23
β-strand	30	1	21
β-strand	33-38	6	22
α-helix	43-47	5
β-strand	56-57	2	23
β-strand	61-66	6	22
β-strand	81-82	2	23
β-strand	93-98	6	22
β-strand	111-112	2	23
β-strand	117-122	6	22
α-helix	133-136	4
β-strand	137	1	23
β-strand	144-148	5	22
α-helix	149-152	4
β-strand	171-173	3	24
β-strand	178-180	3	24
β-strand	182-184	3	25
β-strand	187-188	2	25
β-strand	201	1	26
β-strand	207	1	26
β-strand	213	1	27
β-strand	215	1	27
β-strand	216	1	28
α-helix	222-224	3
β-strand	225	1	28
β-strand	231-233	3	29
β-strand	236-238	3	29
β-strand	245-248	4	29
β-strand	252-255	4	29
α-helix	256-267	12
β-strand	278-280	3	29
β-strand	283-285	3	29
β-strand	292-294	3	30
β-strand	300	1	29
β-strand	301-303	3	30
α-helix	304	1
β-strand	311-312	2	31
α-helix	313-314	2
α-helix	315-317	3
β-strand	318-321	4	32
α-helix	324-328	5
β-strand	335-336	2	31
β-strand	339-342	4	32
α-helix	351-357	7
β-strand	363-364	2	31
β-strand	368-370	3	32
β-strand	378	1	33
β-strand	387-388	2	31
β-strand	394	1	32
β-strand	398-403	6	32
β-strand	410	1	33
β-strand	420-421	2	31
β-strand	425-429	5	32
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	32
β-strand	472-473	2	34
β-strand	475-480	6	35
β-strand	485-489	5	35
α-helix	497-499	3
β-strand	500-509	10	34
β-strand	530-534	5	34
α-helix	535-539	5
β-strand	553-555	3	35
β-strand	563-572	10	34
β-strand	584-585	2	34
β-strand	588-591	4	34
α-helix	599-600	2
β-strand	601-607	7	36
β-strand	613-618	6	36
β-strand	629-637	9	37
α-helix	638-640	3
α-helix	641-644	4
α-helix	706-715	10
β-strand	761-764	4	37
β-strand	769-772	4	36
β-strand	780-788	9	37
β-strand	797	1	37
β-strand	801-806	6	37
α-helix	807-810	4
α-helix	812-814	3
β-strand	817-824	8	38
β-strand	830-835	6	38
β-strand	844-853	10	39
β-strand	859-864	6	39
α-helix	865-871	7
β-strand	874-876	3	38
β-strand	882-892	11	39
β-strand	896	1	39
α-helix	898-902	5
β-strand	903-907	5	39

Chain C: 4 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	40
α-helix	58	1
α-helix	59-63	5
α-helix	72-74	3
β-strand	75	1	40

Chain D: 5 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	8-18	11
β-strand	24	1	41
α-helix	58-62	5
α-helix	65-67	3
α-helix	68-71	4
α-helix	72-74	3
β-strand	75	1	41

Chain E: 4 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	8-18	11
β-strand	24	1	42
α-helix	57-58	2
α-helix	59-63	5
α-helix	68-72	5
β-strand	75	1	42

Chain F: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-18	10
α-helix	58-62	5
α-helix	72-74	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1345	Mus musculus	P15208 (AlphaFold model)
Insulin	C, D, E, F	protein	110	Homo sapiens	P01308 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8EYY_1 Insulin receptor (chains A, B)
HLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDY
LLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIE
KNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVE
RCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVET
CPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLM
CTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGL
IEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLT
ITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRT
SFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRS
NDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVP
LDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTW
SPPFESDDSQKHNQSEYDDSASESSSSPKTDSQILKELEESSFRKTFEDYLHNVVFVPRP
SRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTG
YRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEP
NGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWT
EPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNP
EYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVK
TVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRS
LRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGD
FGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPY
QGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPS
FPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDE
HIPYTHMNGGKKNGRVLTLPRSNPS

Sequence of entity 2 (C, D, E, F), FASTA

>8EYY_2 Insulin (chains C, D, E, F)
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN

Primary citation

Molecular basis for the role of disulfide-linked alpha CTs in the activation of insulin-like growth factor 1 receptor and insulin receptor. Li, J., Wu, J., Hall, C. et al. Elife (2022) 11. DOI 10.7554/eLife.81286 · 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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