7STI: Full-length insulin receptor

Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation. Determined by electron microscopy at 4.9 Å resolution. Released 30 Mar 2022.

Method: Electron microscopy
Resolution: 4.9 Å
Organisms: Mus musculus, Homo sapiens
Chains: 3
Atoms: 13,531
Mol. weight: 323.57 kDa
Released: 30 Mar 2022

Explore 7STI in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7STI contains 44 α-helices and 149 β-strands across 3 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: 18 helices, 79 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	1
β-strand	9-13	5	2
α-helix	19-23	5
β-strand	26	1	1
β-strand	28-29	2	3
β-strand	30-38	9	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	144-148	5	2
β-strand	171-173	3	5
β-strand	178-180	3	5
β-strand	182	1	6
β-strand	188	1	6
β-strand	201	1	7
β-strand	207	1	7
β-strand	212	1	8
β-strand	213	1	9
β-strand	215	1	9
β-strand	216	1	10
α-helix	222-224	3
β-strand	225	1	10
β-strand	228	1	8
β-strand	231-233	3	11
β-strand	236-238	3	11
β-strand	246-248	3	11
β-strand	252-254	3	11
α-helix	256-267	12
β-strand	279	1	12
β-strand	283	1	11
β-strand	293-294	2	13
β-strand	300	1	12
β-strand	301-302	2	13
β-strand	310-312	3	14
β-strand	318-319	2	15
α-helix	325-327	3
β-strand	333-336	4	14
β-strand	339-342	4	15
α-helix	352-357	6
β-strand	363-364	2	14
β-strand	368-371	4	15
β-strand	378	1	16
β-strand	387-388	2	17
β-strand	394	1	18
β-strand	398	1	18
β-strand	400-403	4	15
β-strand	410	1	16
β-strand	420-421	2	17
β-strand	425	1	18
β-strand	428-429	2	15
α-helix	436-445	10
β-strand	457	1	15
β-strand	472-473	2	19
β-strand	475-480	6	20
β-strand	485-489	5	20
α-helix	497-499	3
β-strand	500-509	10	19
β-strand	531-534	4	19
α-helix	535-538	4
β-strand	551-553	3	20
β-strand	561-570	10	19
β-strand	582-583	2	19
β-strand	586-589	4	19
α-helix	597-598	2
β-strand	599-605	7	21
β-strand	611-616	6	21
β-strand	627-635	9	22
α-helix	636-638	3
α-helix	689-713	25
β-strand	759-762	4	22
β-strand	767-770	4	21
β-strand	778-786	9	22
β-strand	795	1	22
β-strand	799-804	6	22
α-helix	805-808	4
β-strand	813	1	23
α-helix	817-818	2
β-strand	819-822	4	24
β-strand	828-831	4	24
β-strand	842-847	6	25
β-strand	859-862	4	25
α-helix	863-869	7
β-strand	872-874	3	24
α-helix	877-878	2
β-strand	881	1	26
β-strand	886-890	5	25
β-strand	894	1	25
β-strand	896	1	23
α-helix	897-899	3
β-strand	904	1	26

Chain B: 21 helices, 68 β-strands

Element	Residues	Length	Sheet
β-strand	12-14	3	27
α-helix	18-23	6
β-strand	29	1	28
β-strand	32-38	7	27
α-helix	43-45	3
β-strand	56-57	2	28
β-strand	60-66	7	27
α-helix	72-74	3
β-strand	81-82	2	28
β-strand	93-96	4	27
β-strand	111-112	2	28
β-strand	117-122	6	27
α-helix	133-135	3
β-strand	137	1	28
β-strand	144-148	5	27
β-strand	171-173	3	29
β-strand	178-180	3	29
β-strand	201	1	30
β-strand	207	1	30
β-strand	212-216	5	31
α-helix	222-224	3
β-strand	225-228	4	31
β-strand	231-232	2	32
β-strand	237-238	2	32
α-helix	241-242	2
α-helix	245	1
β-strand	246-248	3	32
β-strand	252-254	3	32
α-helix	256-267	12
β-strand	279	1	33
β-strand	283	1	32
β-strand	292-294	3	34
β-strand	300	1	33
β-strand	301-303	3	34
α-helix	304	1
β-strand	311-321	11	35
α-helix	325-328	4
β-strand	335-342	8	35
α-helix	351-357	7
β-strand	363-364	2	35
β-strand	368-371	4	35
β-strand	378	1	36
β-strand	387-388	2	35
α-helix	393	1
β-strand	394	1	37
β-strand	398	1	37
β-strand	400-403	4	35
β-strand	410	1	36
β-strand	420-421	2	35
β-strand	425	1	37
β-strand	428-429	2	35
β-strand	431	1	38
α-helix	436-445	10
α-helix	449-451	3
β-strand	457	1	35
β-strand	462	1	38
β-strand	472-473	2	39
β-strand	477-478	2	40
β-strand	485-488	4	40
β-strand	502-509	8	39
β-strand	530-534	5	39
α-helix	535-538	4
β-strand	551-553	3	40
β-strand	560-569	10	39
β-strand	582-583	2	39
β-strand	586-590	5	39
α-helix	597	1
β-strand	598-605	8	41
β-strand	611-618	8	41
β-strand	627-634	8	42
α-helix	639-641	3
α-helix	689-711	23
β-strand	759-762	4	42
β-strand	767-770	4	41
β-strand	778-788	11	42
β-strand	794-795	2	42
β-strand	799-804	6	42
α-helix	805-807	3
β-strand	818-822	5	43
β-strand	828-832	5	43
β-strand	842-850	9	44
β-strand	856-862	7	44
α-helix	863-868	6
β-strand	872-874	3	43
β-strand	882	1	45
β-strand	883-890	8	44
β-strand	894	1	44
α-helix	896-900	5
β-strand	903	1	45

Chain C: 5 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	46
α-helix	58	1
α-helix	59-63	5
α-helix	68-71	4
α-helix	72-74	3
β-strand	75	1	46

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1372	Mus musculus	P15208 (AlphaFold model)
Insulin	C	protein	110	Homo sapiens	P01308 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7STI_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), FASTA

>7STI_2 Insulin (chains C)
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN

Primary citation

Synergistic activation of the insulin receptor via two distinct sites. Li, J., Park, J., Mayer, J.P. et al. Nat Struct Mol Biol (2022) 29:357-368. DOI 10.1038/s41594-022-00750-6 · 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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