8DTL: Insulin receptor

Cryo-EM structure of insulin receptor (IR) bound with S597 peptide. Determined by electron microscopy at 5.4 Å resolution. Released 7 Sept 2022.

Method: Electron microscopy
Resolution: 5.4 Å
Organisms: synthetic construct, Mus musculus
Chains: 4
Atoms: 12,512
Mol. weight: 314.04 kDa
Released: 7 Sept 2022

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

Secondary structure: helices and β-sheets

8DTL contains 46 α-helices and 138 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.

Chains A and B: 20 helices, 69 β-strands

Element	Residues	Length	Sheet
β-strand	6-9	4	1
β-strand	12-14	3	2
α-helix	18-25	8
β-strand	26-30	5	1
β-strand	33-38	6	2
α-helix	43-45	3
β-strand	56-57	2	1
β-strand	61-66	6	2
α-helix	72-75	4
β-strand	81-82	2	1
β-strand	91-96	6	2
β-strand	111-112	2	1
β-strand	116-120	5	2
β-strand	144	1	2
β-strand	171	1	3
β-strand	180	1	3
β-strand	182	1	4
β-strand	188	1	4
α-helix	194-196	3
β-strand	201	1	5
β-strand	207	1	5
β-strand	212-216	5	6
α-helix	222-224	3
β-strand	225-228	4	6
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	256-263	8
β-strand	279	1	8
β-strand	283	1	7
β-strand	292-295	4	8
β-strand	300-303	4	8
β-strand	311-321	11	9
α-helix	324-328	5
β-strand	335-342	8	9
α-helix	351-357	7
β-strand	363-364	2	9
β-strand	368-371	4	9
β-strand	378	1	10
β-strand	387-388	2	9
β-strand	394	1	9
β-strand	398-403	6	9
β-strand	410	1	10
β-strand	420-421	2	9
β-strand	425-426	2	9
β-strand	428	1	11
β-strand	429	1	9
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	11
β-strand	471-473	3	12
β-strand	475-480	6	13
β-strand	485-489	5	13
α-helix	497-499	3
β-strand	502-509	8	12
β-strand	532-534	3	12
α-helix	535-538	4
β-strand	552-555	4	13
β-strand	563-571	9	12
β-strand	583-585	3	12
α-helix	586-587	2
β-strand	588-591	4	12
α-helix	592-594	3
β-strand	604-606	3	14
β-strand	613-616	4	14
α-helix	618-620	3
β-strand	629-633	5	15
β-strand	636-637	2	15
α-helix	638-640	3
α-helix	641-644	4
β-strand	761-764	4	15
β-strand	769-772	4	14
β-strand	780-788	9	15
β-strand	797	1	15
β-strand	801-806	6	15
α-helix	807-810	4
β-strand	815	1	16
β-strand	821-824	4	17
β-strand	830-833	4	17
β-strand	844-851	8	18
β-strand	859-864	6	18
α-helix	865-871	7
β-strand	874-876	3	17
β-strand	883-892	10	18
β-strand	895-896	2	18
β-strand	898	1	16
α-helix	899-901	3
β-strand	903-906	4	18

Chains C and D: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	3-9	7
α-helix	10-14	5
α-helix	23-29	7

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin mimetic peptide S597	C, D	protein	31	synthetic construct
Insulin receptor	A, B	protein	1345	Mus musculus	P15208 (AlphaFold model)

Sequence of entity 1 (C, D), FASTA

>8DTL_1 Insulin mimetic peptide S597 (chains C, D)
SLEEEWAQIECEVYGRGCPSESFYDWFERQL

Sequence of entity 2 (A, B), FASTA

>8DTL_2 Insulin receptor (chains A, B)
HLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDY
LLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIE
KNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVE
RCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVET
CPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLM
CTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGL
IEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLT
ITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRT
SFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRS
NDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVP
LDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTW
SPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRP
SRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTG
YRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEP
NGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWT
EPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNP
EYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVK
TVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRS
LRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGD
FGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPY
QGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPS
FPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDE
HIPYTHMNGGKKNGRVLTLPRSNPS

Primary citation

Activation of the insulin receptor by an insulin mimetic peptide. Park, J., Li, J., Mayer, J.P. et al. Nat Commun (2022) 13:5594-5594. DOI 10.1038/s41467-022-33274-0 · 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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