8EZ0: 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) Symmetric conformation. Determined by electron microscopy at 3.7 Å resolution. Released 9 Nov 2022.

Method: Electron microscopy
Resolution: 3.7 Å
Organisms: Mus musculus, Homo sapiens
Chains: 6
Atoms: 14,640
Mol. weight: 354.33 kDa
Released: 9 Nov 2022

Explore 8EZ0 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8EZ0 contains 60 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, 73 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	1
β-strand	11-13	3	2
α-helix	17-22	6
β-strand	26	1	1
β-strand	28-29	2	3
β-strand	33-38	6	2
α-helix	43-45	3
β-strand	56-57	2	3
β-strand	61-66	6	2
β-strand	71	1	4
β-strand	81-82	2	3
β-strand	93-96	4	2
β-strand	103	1	4
β-strand	111-112	2	3
β-strand	117-122	6	2
α-helix	133-135	3
β-strand	137	1	3
β-strand	144-148	5	2
α-helix	149-152	4
α-helix	169-170	2
β-strand	171-173	3	5
β-strand	178-180	3	5
β-strand	184	1	6
β-strand	187	1	6
β-strand	201	1	7
β-strand	207	1	7
β-strand	212-216	5	8
α-helix	222-224	3
β-strand	225-228	4	8
β-strand	232	1	9
β-strand	237	1	9
β-strand	246-248	3	9
β-strand	252-254	3	9
α-helix	256-267	12
β-strand	278-280	3	9
β-strand	283-285	3	9
β-strand	292-294	3	10
β-strand	300	1	9
β-strand	301-303	3	10
α-helix	304	1
β-strand	311-312	2	11
α-helix	315-317	3
β-strand	319-321	3	12
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-336	2	11
β-strand	340-342	3	12
α-helix	351-357	7
β-strand	363-364	2	11
β-strand	368-371	4	12
β-strand	378	1	13
β-strand	387-388	2	11
β-strand	394	1	12
β-strand	398-403	6	12
β-strand	410	1	13
β-strand	420-421	2	11
β-strand	425-429	5	12
α-helix	436-446	11
β-strand	457	1	12
β-strand	472-473	2	14
β-strand	475	1	15
β-strand	479	1	16
β-strand	486-487	2	16
β-strand	489	1	15
α-helix	497-499	3
β-strand	500-509	10	14
β-strand	530-534	5	14
β-strand	553-554	2	16
β-strand	563-572	10	14
β-strand	584-585	2	14
β-strand	588-591	4	14
α-helix	599-600	2
β-strand	601-609	9	17
β-strand	612-618	7	17
β-strand	629-637	9	18
α-helix	638-640	3
α-helix	641-644	4
α-helix	691-715	25
β-strand	761-765	5	18
β-strand	769-773	5	17
β-strand	780-788	9	18
α-helix	799-800	2
β-strand	801-805	5	18
α-helix	807-809	3
β-strand	817-824	8	19
β-strand	829-835	7	19
β-strand	844-851	8	20
β-strand	853	1	21
β-strand	859-864	6	20
α-helix	865-871	7
β-strand	874-877	4	19
α-helix	879-880	2
β-strand	882-886	5	21
β-strand	887-892	6	20
β-strand	903-907	5	21

Chain B: 25 helices, 76 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	22
β-strand	11-13	3	23
α-helix	17-22	6
β-strand	26	1	22
β-strand	28-29	2	24
β-strand	33-38	6	23
α-helix	43-45	3
β-strand	56-57	2	24
β-strand	61-66	6	23
β-strand	71	1	25
β-strand	81-82	2	24
β-strand	93-96	4	23
β-strand	103	1	25
β-strand	111-112	2	24
β-strand	117-122	6	23
α-helix	133-135	3
β-strand	137	1	24
β-strand	144-148	5	23
α-helix	149-152	4
β-strand	172-173	2	26
β-strand	178-179	2	26
β-strand	182	1	27
β-strand	188	1	27
β-strand	201	1	28
β-strand	207	1	28
β-strand	212-216	5	29
α-helix	222-224	3
β-strand	225-228	4	29
β-strand	231-233	3	30
β-strand	236-238	3	30
α-helix	241-242	2
α-helix	245	1
β-strand	246-248	3	30
β-strand	252-254	3	30
α-helix	256-267	12
β-strand	278-280	3	30
β-strand	283-285	3	30
β-strand	292-294	3	31
β-strand	300	1	30
β-strand	301-303	3	31
α-helix	304	1
β-strand	311-312	2	32
α-helix	315-317	3
β-strand	319-321	3	33
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-336	2	32
β-strand	340-342	3	33
α-helix	351-357	7
β-strand	363-364	2	32
β-strand	368-371	4	33
β-strand	378	1	34
α-helix	379-381	3
β-strand	387-388	2	32
β-strand	394	1	33
β-strand	398-403	6	33
β-strand	410	1	34
β-strand	420-421	2	32
β-strand	425-426	2	33
β-strand	428	1	35
β-strand	429	1	33
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	35
β-strand	472-473	2	36
β-strand	475	1	37
β-strand	479	1	38
β-strand	486-487	2	38
β-strand	489	1	37
β-strand	500-509	10	36
β-strand	530-534	5	36
β-strand	553-554	2	38
β-strand	563-572	10	36
β-strand	584-585	2	36
β-strand	588-591	4	36
α-helix	599-600	2
β-strand	601-609	9	39
β-strand	612-618	7	39
β-strand	629-636	8	40
α-helix	638-640	3
α-helix	641-644	4
α-helix	694-715	22
β-strand	761-765	5	40
β-strand	769-773	5	39
β-strand	780-788	9	40
α-helix	799-800	2
β-strand	801-806	6	40
α-helix	807-809	3
β-strand	821-824	4	41
β-strand	829-833	5	41
β-strand	844-852	9	42
β-strand	853	1	43
β-strand	858-863	6	42
α-helix	865-871	7
β-strand	874-877	4	41
α-helix	879-880	2
β-strand	882-886	5	43
β-strand	887-892	6	42
β-strand	896	1	42
α-helix	897-899	3
β-strand	903-907	5	43

Chain D: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-18	10
α-helix	58-62	5
α-helix	68-72	5

Chain E: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-18	10
α-helix	57	1
α-helix	58-63	6
α-helix	68-72	5

Chains F and G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-18	10
α-helix	58-63	6
α-helix	68-73	6

Molecules and chains

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

Sequence of entity 1 (A, B), FASTA

>8EZ0_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 (D, E, F, G), FASTA

>8EZ0_2 Insulin (chains D, E, F, G)
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)…
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…
7STI 4.9 Å, Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound)…

Browse structure collections

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